Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4(+) T cells
ABSTRACT Although substantial evidence suggests that T cells are important in the pathogenesis of atopic dermatitis (AD), little is known of the differentiation status of CD4+ T cells specific for common environmental allergens.
To determine the frequency, differentiation phenotype, and function of circulating allergen-specific CD4+ T cells in adult individuals with severe persistent AD and controls.
Using tetrameric complexes of an HLA DRB1*0101 restricted epitope from Fel d 1, the major IgE-reactive component of cat dander, we studied ex vivo and cultured T-cell frequency and phenotype in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IFN-gamma, IL-4, and IL-10 enzyme linked immuno-spot analysis.
Ex vivo Fel d 1-specific DRB1*0101-restricted CD4+ T cells express high levels of CCR7, CD62L, CD27, and CD28 and proportionately low levels of tissue-specific homing receptors and TH1 and TH2 cytokine production, placing the cells largely within the central memory subgroup.
Circulating Fel d 1-specific DRB1*0101-restricted CD4+ T cells maintain central memory capacity, consistent with a potential to contribute to persisting clinical atopic disease.
Persisting central memory characteristics of allergen-specific CD4+ T cells in individuals with AD may contribute to chronic disease.
- SourceAvailable from: Kirsten Freitag[Show abstract] [Hide abstract]
ABSTRACT: Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+) CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4(+) T cells directed against MTB.Scandinavian Journal of Immunology 06/2007; 65(5):467-78. DOI:10.1111/j.1365-3083.2007.01924.x · 1.88 Impact Factor
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ABSTRACT: This article reviews the progress in the field of basic and clinical immunology in 2006, focusing on the articles published in the Journal. The role of Toll-like receptors in the immune response was explored in detail in several articles. The knowledge gained in these investigations is being used to develop strategies that enhance the immunogenicity of vaccines to prevent infectious diseases and to have an immunomodulatory effect on allergic diseases. Other components of the innate immunity reported on were the recognition of allergens with lipid-derived motifs by CD1d-restricted T cells and the role of dendritic cells in the development of an allergic response. More than 120 primary immunodeficiencies were defined at a molecular level, and biological agents such as TNF-alpha antagonists and IFN-alpha were shown to have therapeutic use. New anti-HIV drugs that block cell entry were proven to be effective, thus offering alternative therapies to respond to the development of multidrug-resistant HIV strains. The modern understanding of immunologic concepts is helping to elucidate the mechanisms of defense against viruses, bacteria, and parasites; as a result, strategies to improve management and prevention continue to emerge.Journal of Allergy and Clinical Immunology 09/2007; 120(2):263-70. DOI:10.1016/j.jaci.2007.05.031 · 11.25 Impact Factor