Susan Kovats

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States

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Publications (33)247.74 Total impact

  • Esther Carreras, Susan Kovats
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    ABSTRACT: Although some hematopoietic cell types are known to respond to sex hormones, hematopoietic stem cells (HSCs) are generally thought to function similarly in both sexes. Recently in Nature, Nakada et al. (2014) show that HSCs respond to higher levels of estrogen in females, resulting in enhanced self-renewal and increased erythropoiesis.
    Cell stem cell 02/2014; 14(2):137-8. · 23.56 Impact Factor
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    ABSTRACT: E protein transcription factors and their natural inhibitors, Id proteins, play critical and complex roles during lymphoid development. In this article, we report that partial maintenance of E protein activity during positive selection results in a change in the cell fate determination of developing iNKT cells, with a block in the development of iNKT1 cells and a parallel increase in the iNKT2 and iNKT17 subsets. Because the expression levels of the transcription factors that drive these alternative functional fates (GATA-3, RORγT, T-bet, and Runx-3) are not altered, our results suggest that E protein activity controls a novel checkpoint that regulates the number of iNKT precursors that choose each fate.
    The Journal of Immunology 10/2013; · 5.52 Impact Factor
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    ABSTRACT: Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b(+) splenic DC. We found that the skin of naive IRF4(-/-) mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b(+) and CD103(+) dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency. In contrast, numbers of migratory eLC and CD11b(+) dDC were significantly reduced in the cutaneous LN of IRF4(-/-) mice, suggesting a defect in constitutive migration from the dermis during homeostasis. Upon induction of skin inflammation, CD11b(+) dDC in IRF4(-/-) mice did not express the chemokine receptor CCR7 and failed to migrate to cutaneous LN, whereas the migration of eLC was only mildly impaired. Thus, although dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b(+) dDC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity.
    The Journal of Immunology 08/2012; 189(7):3368-77. · 5.52 Impact Factor
  • Susan Kovats
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    ABSTRACT: This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and Disease." Immune cells and hematopoietic progenitors express estrogen receptors (ER). As ligand-activated transcription factors that modulate chromatin structure, ER regulate transcriptional programs that direct the development or functional responses of immune cells. ER-regulated immune responses likely contribute to significant sex biases in infection, autoimmunity and other inflammatory diseases, and changes in immune function during the female hormonal cycle and pregnancy. Here we summarize our own and others' studies showing that ERα signaling regulates the development of dendritic cells (DCs), antigen-presenting cells crucial for initiation of innate and adaptive immunity. During inflammation, elevated GM-CSF directs the development of new DCs from monocytes or other precursors that infiltrate tissues and lymphoid organs, and these de novo populations of inflammatory DCs have critical roles in programming T cell-mediated responses during infection and autoimmunity. Estradiol acting via ERα, but not ERβ, promotes the GM-CSF-mediated inflammatory pathway of DC differentiation, leading to the development of DCs with increased functional capacity. Estradiol/ERα signaling acts directly in GM-CSF-stimulated myeloid progenitors to induce elevated levels of IRF4, a transcription factor that directs a developmental program underlying CD11b(+) DC differentiation. In contrast, during homeostatic Flt3 Ligand-driven DC development, ERα signaling decreases numbers of myeloid progenitors and differentiated DCs, yet promotes more functionally competent DCs. Thus ERα signaling regulates the response of DC progenitors to the external cytokine environment, thereby altering the strength or integrity of DC developmental pathways. The development of increased numbers of DCs during inflammation will likely increase the magnitude of DC-mediated functional responses including cytokine production, processing and MHC-mediated presentation of antigens, and activation and polarization of T and B lymphocytes; these functions also may be regulated directly by ERα signaling. In sum, via profound effects on DC development and ensuing functional responses, ERα signaling can regulate the quality of the adaptive immune responses and influence the resolution of infection or chronic inflammatory diseases.
    Hormones and Behavior 04/2012; 62(3):254-62. · 3.74 Impact Factor
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    ABSTRACT: CD1d-restricted type I NKT cells provide help for specific antibody production. B cells, which have captured and presented a T-dependent, antigen-derived peptide on MHC class II and CD1d-binding glycolipid α-GC on CD1d, respectively, activate Th and NKT cells to elicit B cell help. However, the role of the DC CD1d in humoral immunity remains unknown. We therefore constructed mixed bone marrow chimeras containing CD1d-expressing, DTR-transgenic DCs and CD1d(+) or CD1d(-) nontransgenic DCs. Following DT-mediated DC ablation and immunization, we observed that the primary and secondary antibody responses were equivalent in the presence of CD1d(+) and CD1d(-) DCs. In contrast, a total ablation of DCs delayed the primary antibody response. Further experiments revealed that depletion of CD1d(+) DCs blocked in vivo expansion of antigen-specific cytotoxic (CD8(+)) T lymphocytes. These results provide a clear demonstration that although CD1d expression on DCs is essential for NKT-enhanced CD8(+) T cell expansion, it is dispensable for specific antibody production.
    Journal of leukocyte biology 02/2012; 91(5):783-90. · 4.99 Impact Factor
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    ABSTRACT: Type I IFNs are potent regulators of innate and adaptive immunity and are implicated in the pathogenesis of systemic lupus erythematosus. Here we report that clinical and pathological lupus nephritis and serum anti-nuclear Ab levels are greatly attenuated in New Zealand Mixed (NZM) 2328 mice deficient in type I IFN receptors (IFNAR). To determine whether the inflammatory environment in NZM 2328 mice leads to IFNAR-regulated changes in dendritic cells (DC), the number, activation, and function of DC subsets were compared in 2- and 5-mo-old (clinically healthy) female NZM and NZM-IFNAR(-/-) mice. Numbers of activated CD40(high) plasmacytoid DC (pDC) were significantly increased in renal lymph nodes of 2-mo-old NZM but not NZM-IFNAR(-/-) mice, suggesting an early IFNAR-dependent expansion and activation of pDC at disease sites. Relative to NZM spleens, NZM-IFNAR(-/-) spleens in 5-mo-old mice were significantly decreased in size and contained reduced numbers of conventional DC subsets, but not pDC. Splenic and renal lymph node NZM-IFNAR(-/-) DC analyzed directly ex vivo expressed significantly less CD40, CD86, and PDL1 than did NZM DC. Upon activation with synthetic TLR9 ligands in vitro, splenic NZM-IFNAR(-/-) DC produced less IL-12p40/70 and TNF-alpha than did NZM DC. The limited IFNAR(-/-) DC response to endogenous activating stimuli correlated with reduced numbers of splenic activated memory CD4(+) T cells and CD19(+) B cells in older mice. Thus, IFNAR signaling significantly increases DC numbers, acquisition of Ag presentation competence, and proinflammatory function before onset of clinically apparent lupus disease.
    The Journal of Immunology 10/2009; 183(9):6021-9. · 5.52 Impact Factor
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    ABSTRACT: During inflammation, elevated granulocyte macrophage-colony-stimulating factor (GM-CSF) directs the development of new dendritic cells (DCs). This pathway is influenced by environmental factors, and we previously showed that physiologic levels of estradiol, acting through estrogen receptor alpha (ERalpha), promote the GM-CSF-mediated differentiation of a CD11b(+) DC subset from myeloid progenitors (MPs). We now have identified interferon regulatory factor 4 (IRF4), a transcription factor induced by GM-CSF and critical for CD11b(+) DC development in vivo, as a target of ERalpha signaling during this process. In MPs, ERalpha potentiates and sustains GM-CSF induction of IRF4. Furthermore, retroviral delivery of the Irf4 cDNA to undifferentiated ERalpha(-/-) bone marrow cells restored the development of the estradiol/ERalpha-dependent DC population, indicating that an elevated amount of IRF4 protein substitutes for ERalpha signaling. Thus at an early stage in the MP response to GM-CSF, ERalpha signaling induces an elevated amount of IRF4, which leads to a developmental program underlying CD11b(+) DC differentiation.
    Blood 10/2009; 115(2):238-46. · 9.78 Impact Factor
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    Amr H Sawalha, Susan Kovats
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    ABSTRACT: Dehydroepiandrosterone (DHEA) is a weak androgen that exerts pleomorphic effects on the immune system. The hormone has no known receptor, and consequently, its mechanism of action on immunocompetent cells remains poorly understood. Interestingly, serum levels of DHEA are decreased in patients with inflammatory diseases including lupus, and these levels seem to correlate inversely with disease activity. Following encouraging studies demonstrating beneficial effects of DHEA supplementation in murine lupus models, several clinical studies have tested the effect of DHEA in lupus patients. DHEA treatment could improve overall quality-of-life assessment measures and glucocorticoid requirements in some lupus patients with mild to moderate disease; however, DHEA's effect on disease activity in lupus patients remains controversial. Long-term safety studies are required in light of the reported effect of DHEA supplementation in lowering high-density lipoprotein cholesterol in lupus patients.
    Current Rheumatology Reports 09/2008; 10(4):286-91.
  • Susan Kovats
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    ABSTRACT: Gorilla Mountain. The Story of Wildlife Biologist Amy Vedder. Rene Ebersole. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095518. Robo World. The Story of Robot Designer Cynthia Breazeal. Jordan D. Brown. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095563. Nature's Machines. The Story of Biomechanist Mimi Koehl. Deborah Parks. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095594. Three books from the Women's Adventures in Science series present the experiences and research of a wildlife biologist, a robot designer, and a biomechanist to encourage young readers' interests.
    Science 07/2008; 321(5885):39-40. · 31.20 Impact Factor
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    Susan Kovats, Esther Carreras
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    ABSTRACT: Estrogen receptor (ER) ligands can modulate innate and adaptive immunity and hematopoiesis, which may explain the clear sex differences in immune responses during autoimmunity, infection or trauma. Dendritic cells (DC) are antigen presenting cells important for initiation of innate and adaptive immunity, as well as immune tolerance. DC progenitors and terminally differentiated DC express ER, indicating the ER ligands may regulate DC at multiple developmental and functional stages. Although there are profound differences in innate immunity between males and females or upon systemic imposition of sex hormones, studies are just beginning to link these differences to DC. Our and others studies demonstrate that estradiol and other ER ligands regulate the homeostasis of bone marrow myeloid and lymphoid progenitors of DC, as well as DC differentiation mediated by GM-CSF and Flt3 Ligand. Since DC have a brief lifespan, these data suggest that relatively short exposures to ER ligands in vivo will alter DC numbers and intrinsic functional capacity related to their developmental state. Studies in diverse experimental models also show that agonist and antagonist ER ligands modulate DC activation and production of inflammatory mediators. These findings have implications for human health and disease since they suggest that both DC development and functional capacity will be responsive to the physiological, pharmacological and environmental ER ligands to which an individual is exposed in vivo.
    Cellular Immunology 03/2008; 252(1-2):81-90. · 1.74 Impact Factor
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    ABSTRACT: Estrogen receptor (ER) ligands modulate hemopoiesis and immunity in the normal state, during autoimmunity, and after infection or trauma. Dendritic cells (DC) are critical for initiation of innate and adaptive immune responses. We demonstrate, using cytokine-driven culture models of DC differentiation, that 17-beta-estradiol exerts opposing effects on differentiation mediated by GM-CSF and Flt3 ligand, the two cytokines that regulate DC differentiation in vivo. We also show that estradiol acts on the same highly purified Flt3+ myeloid progenitors (MP) to differentially regulate the DC differentiation in each model. In GM-CSF-supplemented cultures initiated from MP, physiological amounts of estradiol promoted differentiation of Langerhans-like DC. Conversely, in Flt3 ligand-supplemented cultures initiated from the same MP, estradiol inhibited cell survival in a dose-dependent manner, thereby decreasing the yield of plasmacytoid and conventional myeloid and lymphoid DC. Experiments with bone marrow cells from ER-deficient mice and the ER antagonist ICI182,780 showed that estradiol acted primarily via ERalpha to regulate DC differentiation. Thus, depending on the cytokine environment, pathways of ER signaling and cytokine receptor signaling can differentially interact in the same Flt3+ MP to regulate DC development. Because the Flt3 ligand-mediated differentiation pathway is important during homeostasis, and GM-CSF-mediated pathways are increased by inflammation, our data suggest that endogenous or pharmacological ER ligands may differentially affect DC development during homeostasis and disease, with consequent effects on DC-mediated immunity.
    The Journal of Immunology 02/2008; 180(2):727-38. · 5.52 Impact Factor
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    ABSTRACT: Several MHC class II alleles linked with autoimmune diseases form unusually low stability complexes with CLIP, leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. To investigate cellular consequences of altering class II/CLIP affinity, we evaluated invariant chain (Ii) mutants with varying CLIP affinity for a mouse class II allele, I-E(d), which has low affinity for wild-type CLIP and is associated with a mouse model of spontaneous, autoimmune joint inflammation. Increasing CLIP affinity for I-E(d) resulted in increased cell surface and total cellular abundance and half-life of I-E(d). This reveals a post-endoplasmic reticulum chaperoning capacity of Ii via its CLIP peptides. Quantitative effects on I-E(d) were less pronounced in DM-expressing cells, suggesting complementary chaperoning effects mediated by Ii and DM, and implying that the impact of allelic variation in CLIP affinity on immune responses will be highest in cells with limited DM activity. Differences in the ability of cell lines expressing wild-type or high-CLIP-affinity mutant Ii to present Ag to T cells suggest a model in which increased CLIP affinity for class II serves to restrict peptide loading to DM-containing compartments, ensuring proper editing of antigenic peptides.
    The Journal of Immunology 12/2007; 179(9):5907-15. · 5.52 Impact Factor
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    ABSTRACT: To assess the ability of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to function as antigen-presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues. Human class II major histocompatibility complex (MHC)-typed FLS were used as APCs for murine class II MHC-restricted CD4 T cell hybridomas. Interferon-gamma (IFNgamma)-treated, antigen-loaded FLS were cocultured with T cell hybridomas specific for immunodominant portions of human cartilage gp-39 (HC gp-39) or human type II collagen (CII). T cell hybridoma activation was measured by enzyme-linked immunosorbent assay of culture supernatants for interleukin-2. Both synthetic peptide and synovial fluid (SF) were used as sources of antigen. APC function in cocultures was inhibited by using blocking antibodies to human class II MHC, CD54, or CD58, or to murine CD4, CD11a, or CD2. Human FLS could present peptides from the autoantigens HC gp-39 and human CII to antigen-specific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFNgamma, showed MHC restriction, and was dependent on human class II MHC and murine CD4 for effective antigen presentation. Furthermore, FLS were able to extract and present antigens found within human SF to both the HC gp-39 and human CII T cell hybridomas in an IFNgamma-dependent and MHC-restricted manner. RA FLS can function as APCs and are able to present peptides derived from autoantigens found within joint tissues to activated T cells in vitro. In the context of inflamed synovial tissues, FLS may be an important and hitherto overlooked subset of APCs that could contribute to autoreactive immune responses.
    Arthritis & Rheumatology 06/2007; 56(5):1497-506. · 7.48 Impact Factor
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    ABSTRACT: The steroid hormone estrogen regulates the differentiation, survival, or function of diverse immune cells. Previously, we found that physiological amounts of 17beta-estradiol act via estrogen receptors (ER) to promote the GM-CSF-mediated differentiation of dendritic cells (DC) from murine bone marrow progenitors in ex vivo cultures. Of the two major subsets of CD11c(+) DC that develop in these cultures, estrogen is preferentially required for the differentiation of a CD11b(int)Ly6C(-) population, although it also promotes increased numbers of a CD11b(high)Ly6C(+) population. Although both DC subsets express ERalpha, only the CD11b(high)Ly6C(+) DC express ERbeta, perhaps providing a foundation for the differential regulation of these two DC types by estrogen. The two DC populations exhibit distinct phenotypes in terms of capacity for costimulatory molecule and MHC expression, and Ag internalization, which predict functional differences. The CD11b(int)Ly6C(-) population shows the greatest increase in MHC and CD86 expression after LPS activation. Most notably, the estrogen-dependent CD11b(int)Ly6C(-) DC express langerin (CD207) and contain Birbeck granules characteristic of Langerhans cells. These data show that estrogen promotes a DC population with the unique features of epidermal Langerhans cells and suggest that differentiation of Langerhans cells in vivo will be dependent upon local estrogen levels and ER-mediated signaling events in skin.
    The Journal of Immunology 11/2005; 175(8):5146-51. · 5.52 Impact Factor
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    ABSTRACT: Most immune cells, including myeloid progenitors and terminally differentiated dendritic cells (DC), express estrogen receptors (ER) making these cells sensitive to estrogens. Our laboratory recently demonstrated that 17-beta-estradiol (E2) promotes the GM-CSF-mediated development of CD11c+ CD11b(int) DC from murine bone marrow precursors. We tested whether the therapeutic selective estrogen receptor modulators (SERM), raloxifene and tamoxifen, can perturb DC development and activation. SERM, used in treatment of breast cancer and osteoporosis, bind to ER and mediate tissue-specific agonistic or antagonistic effects. Raloxifene and tamoxifen inhibited the differentiation of estrogen-dependent DC from bone marrow precursors ex vivo in competition experiments with physiological levels of E2. DC differentiated in the presence of SERM were assessed for their capacity to internalize fluoresceinated Ags as well as respond to inflammatory stimuli by increasing surface expression of molecules important for APC function. Although SERM-exposed DC exhibited increased ability to internalize Ags, they were hyporesponsive to bacterial LPS: relative to control DC, they less efficiently up-regulated the expression of MHC class II, CD86, and to a lesser extent, CD80 and CD40. This phenotype indicates that these SERM act to maintain DC in an immature state by inhibiting DC responsiveness to inflammatory stimuli. Thus, raloxifene and tamoxifen impair E2-promoted DC differentiation and reduce the immunostimulatory capacity of DC. These observations suggest that SERM may depress immunity when given to healthy individuals for the prevention of osteoporosis and breast cancer and may interfere with immunotherapeutic strategies to improve antitumor immunity in breast cancer patients.
    The Journal of Immunology 09/2005; 175(4):2666-75. · 5.52 Impact Factor
  • Greg Nalbandian, Susan Kovats
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    ABSTRACT: The initiation and perpetuation of innate and adaptive immunity is dependent on the ability of professional antigen-presenting cells (APCs) to sense inflammatory stimuli; produce cytokines; and internalize, degrade, and present antigens via surface major histocompatibility complex (MHC) molecules. Dendritic cells (DCs), macrophages, and B lymphocytes express estrogen receptors, indicating that the steroid sex hormone estrogen might directly modulate the function of these cells during immune responses. Sex-specific parameters of immune function have been identified during autoimmunity and the pathogenesis of infectious disease, which show sex biases in their incidence and manifestation; female immunity also varies as estrogen levels change. In this article, we summarize studies that demonstrate effects of estrogen on the differentiation or function of APCs in model in vitro systems, or under circumstances of natural or imposed variation in estrogen levels in vivo.
    Immunologic Research 02/2005; 31(2):91-106. · 3.53 Impact Factor
  • Greg Nalbandian, Susan Kovats
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    ABSTRACT: Sex biases in autoimmunity and infection, together with immune cell expression of estrogen and androgen receptors, suggest that sex steroid hormones directly modulate immune cells, although the mechanism(s) by which this might occur is not completely understood. The female predisposition to autoimmunity, and alteration of disease symptoms during pregnancy, has led to the idea that lower physiological amounts of estrogen are stimulatory to the immune system, while pharmacological doses or pregnancy levels of estrogen modulate cell mediated immunity. These differences in immune function during naturally occurring variation in estrogen levels have been corroborated through studies of exogenous estrogen treatment in vivo or in vitro. The resolution of immune responses is dependent upon the nature of soluble mediators produced by the innate and adaptive immune system, and estrogen modulation of cytokine and chemokine profiles often correlates with amelioration or exacerbation of autoimmunity. In this review, we will summarize recently published studies that demonstrate effects of estrogen on autoimmune responses in humans and in murine model systems, with a focus on CD4+ T helper cell differentiation and cytokine production, B cell function and autoantibody production, hematopoietic cell differentiation and proinflammatory estrogen metabolites. It is of interest to understand the effects of estrogens on both normal immunity and autoimmune disease models because both estrogens and selective estrogen receptor modulators currently are being assessed for clinical efficacy in the treatment of autoimmunity and cancer.
    Current Medicinal Chemistry - Immunology Endocrine & Metabolic Agents 01/2005; 5(1):85-91.
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    ABSTRACT: Sex biases in autoimmunity and infection suggest that steroid sex hormones directly modulate immune cells. We show in this study that 17-beta-estradiol (E2) promotes the differentiation of functional dendritic cells (DC) from murine bone marrow precursor cells. Remarkably, ex vivo DC differentiation was inhibited in steroid hormone-deficient medium, and was restored by addition of physiological amounts of E2, but not dihydrotestosterone. DC differentiation was inhibited by the estrogen receptor (ER) antagonists ICI 182,780 and tamoxifen, and from ERalpha(-/-) bone marrow cells, indicating that E2 acted via ERs. E2 addition was most effective in promoting DC differentiation immediately ex vivo, but did not increase DC proliferation. E2 treatment specifically promoted differentiation of a CD11c(+) CD11b(int) DC population that displayed high levels of cell surface MHC class II and CD86, suggesting that E2 could augment numbers of potent APC. DC that differentiated in E2-supplemented medium were fully functional in their capability to mediate presentation of self and foreign Ags and stimulate the proliferation of naive CD4(+) T cells. The requirement for estrogen during DC differentiation suggests a mechanism by which E2 levels in peripheral tissues might modulate both the number and functional capabilities of DC in vivo, thereby influencing immune responses.
    The Journal of Immunology 03/2004; 172(3):1426-36. · 5.52 Impact Factor
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    ABSTRACT: Rheumatoid arthritis is characterized by synovial joint infiltration of activated CD4(+) T cells and MHC class II(+) APC, and is linked to specific HLA-DR alleles. Candidate autoantigens in synovial fluid and cartilage include type II collagen (CII) and cartilage gp39 (HCgp39). Using preparations of native Ag and T cells derived from Ag-immunized DR4-transgenic mice, we determined that human ex vivo differentiated DR4(+) dendritic cells (DC) and macrophages (Mphi) can mediate MHC class II presentation of CII or HCgp39 epitopes. The form of the Ag (soluble, partially degraded, or particulate) delivered to the APC influenced its presentation by DC and Mphi. DC efficiently presented partially degraded, but not native CII alpha-chains, while Mphi presentation was most efficient after phagocytosis of bead-conjugated CII. Both DC and Mphi presented soluble HCgp39, and activated Mphi from some donors presented epitopes derived from endogenously synthesized HCgp39. When synovial fluid from rheumatoid arthritis patients was used as a source of Ag, DC presentation of HCgp39 and CII epitopes was efficient, indicating that synovial fluid contains soluble forms of CII and HCgp39 amenable to internalization, processing, and presentation. These data support the hypothesis that CII and HCgp39 are autoantigens and that their class II-mediated presentation by DC and Mphi to T cells in vivo has a critical role in the pathogenesis of human rheumatoid arthritis.
    The Journal of Immunology 01/2003; 169(11):6625-33. · 5.52 Impact Factor
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    ABSTRACT: We report a strategy for high through-put sequence analyses of large MHC class II-bound peptide repertoires which combines automated electrospray ionization tandem mass-spectrometry with computer-assisted interpretation of the tandem mass spectra using the algorithm SEQUEST. This powerful approach discerned 128 peptide sequences displayed by the murine MHC class II molecule I-Ab in activated B cells and macrophages, including a surprisingly large number of peptides derived from self cytosolic proteins. Mice lacking the chaperone molecule H-2M were used to generate T cells specific for selected self peptides. Functional T cell analyses of ex vivo antigen-presenting cells indicated that peptides originating from cytosolic proteins are efficiently presented by splenic and thymic dendritic cells, but less so by resting B cells or thymic cortical epithelial cells. These results suggest that central tolerance to at least some MHC class II-bound self peptides derived from cytosolic proteins exists in vivo.
    European Journal of Immunology 06/2001; 31(5):1485-94. · 4.97 Impact Factor

Publication Stats

1k Citations
247.74 Total Impact Points

Institutions

  • 2007–2012
    • Oklahoma Medical Research Foundation
      • Arthritis and Clinical Immunology Program
      Oklahoma City, Oklahoma, United States
  • 2003–2007
    • Beckman Research Institute
      Duarte, California, United States
  • 2005
    • City of Hope National Medical Center
      • Department of Immunology
      Duarte, CA, United States
  • 2001
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 1995–2001
    • University of Washington Seattle
      • Department of Immunology
      Seattle, WA, United States
  • 1997
    • Indiana University-Purdue University Indianapolis
      • Department of Microbiology and Immunology
      Indianapolis, IN, United States
  • 1994–1995
    • Virginia Mason Medical Center
      Seattle, Washington, United States