CXCR5 identifies a subset of Vγ9Vδ2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production

Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
The Journal of Immunology (Impact Factor: 4.92). 11/2006; 177(8):5290-5. DOI: 10.4049/jimmunol.177.8.5290
Source: PubMed


Vgamma9Vdelta2 T lymphocytes recognize nonpeptidic Ags and mount effector functions in cellular immune responses against microorganisms and tumors, but little is known about their role in Ab-mediated immune responses. We show here that expression of CXCR5 identifies a unique subset of Vgamma9Vdelta2 T cells which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and IL-10 and help B cells for Ab production. These properties portray CXCR5+ Vgamma9Vdelta2 T cells as a distinct memory T cell subset with B cell helper function.

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Available from: Francesco Dieli
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    • "Indeed, microarray studies revealed that Vc9/Vd2 T cells primed in the presence of IL-21 assume features typically associated with human T FH cells, most notably the expression of the B cell attracting chemokine, CXCL13, which is key in recruiting B cells to secondary lymphoid tissue and establishing germinal centers [74]. On a functional level, activated Vc9/Vd2 T cells readily provide B cell help in vitro, with a particular contribution of Vc9/Vd2 T cell-expressed CD40L and inducible T cell co-stimulator (ICOS) as well as IL-4 and IL-10 [111] [112]. These findings identify an intimate tripartite crosstalk between antigenspecific CD4 + T FH cells, HMB-PP responsive Vc9/Vd2 T cells and follicular B cells in which both CD4 + and cd T cells regulate the recruitment of further cells to the germinal center and the production and affinity maturation of class-switched antibodies [113] [114] (Fig. 1). "
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    ABSTRACT: Unconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vγ9/Vδ2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vγ9/Vδ2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jan 2015 · Cellular Immunology
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    • "Accordingly, Vγ9Vδ2 T cells can also be activated, through an indirect mechanism, by aminobisphosphonates, a class of drugs used to treat certain bone diseases, that inhibit farnesyl pyrophosphate synthase, and cause accumulation of endogenous upstream metabolites such as isopentenylpyrophosphate (IPP) [16]. Vγ9Vδ2 T cells may indirectly contribute to the immune defense against cancer cells, by producing cytokines typical of Th1, Th2 or Th17 cells [17]–[19], or cross-talking with dendritic cells [20], macrophages [21] and B cells [22]–[24]. Additionally, Vγ9Vδ2 T cells perform direct potent cytotoxic activity toward cancer cells, which is mediated in much the same manner as for CD8 T cells and NK cells, through perforin/granzyme, Fas/FasL, TNF/TNF-R and TRAIL-TRAIL-R pathways [10]. "
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    ABSTRACT: Colon cancer comprises a small population of cancer initiating stem cells (CIC) that is responsible for tumor maintenance and resistance to anti-cancer therapies, possibly allowing for tumor recapitulation once treatment stops. Combinations of immune-based therapies with chemotherapy and other anti-tumor agents may be of significant clinical benefit in the treatment of colon cancer. However, cellular immune-based therapies have not been experimented yet in the population of colon CICs. Here, we demonstrate that treatment with low concentrations of commonly used chemotherapeutic agents, 5-fluorouracyl and doxorubicin, sensitize colon CICs to Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 T cell cytotoxicity was largely mediated by TRAIL interaction with DR5, following NKG2D-dependent recognition of colon CIC targets. We conclude that in vivo activation of Vγ9Vδ2 T cells or adoptive administration of ex-vivo expanded Vγ9Vδ2 T cells at suitable intervals after chemotherapy may substantially increase anti-tumor activities and represent a novel strategy for colon cancer immunotherapy.
    Full-text · Article · Jun 2013 · PLoS ONE
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    • "Interestingly, few CD4– T cell subsets expressed ICOS though a majority of them expressed Bcl6 suggesting that these subsets probably localize to the GC rich regions of the LN. Quigley ME et al [32] showed that CXCR5+CD8 T cells frequently infiltrate B cell follicles whereas others have shown that NKT and γδ T cells were present in GC [33], [34], [35], [36]. "
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    ABSTRACT: CD4 T follicular helper (Tfh) cells play a unique and essential role in the generation of B cell responses in the lymph node microenvironment. Here we sought to determine if differential expression of PD-1 could be used to delineate Tfh cells in rhesus macaque lymph nodes (LN). CD3(+)CD4(+) T cells were found to harbor a unique subset of cells that expressed the Program death-1 (PD-1) receptor at significantly high levels that were enriched in the LN compartment as compared to peripheral blood. The LN CD4(+)PD1(hi) T cells expressed a predominantly CD28(+)CD95(+) central memory phenotype and were CCR7(lo)ICOS(hi)Bcl6(hi). Additionally, CD4(+)PD1(hi) T cells preferentially expressed high levels of CXCR5 and IL-21 and significantly correlated with Bcl6(+)Ki-67(+) IgG(+) B cells. As Bcl6 is primarily expressed by proliferating B cells within active germinal centers, our results suggest that LN CD4(+)PD1(hi) T cells likely localize to active GC regions, a characteristic that is attributable to Tfh cells. Overall, our findings suggest that high levels of PD-1 expression on CD4(+) T cells in LN of rhesus macaques can serve as a valuable marker to identify Tfh cells and has implications for studying the role of Tfh cells in Human immunodeficiency virus (HIV), Simian immunodeficiency virus (SIV) and other infectious diseases that use the rhesus macaque model.
    Full-text · Article · Mar 2013 · PLoS ONE
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