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The strong association of HLA B27 with spondyloarthropathies contrasts strikingly with most autoimmune diseases, which are HLA class II associated and thought to be mediated by CD4+ T lymphocytes. By introducing a human-derived HLA B27-restricted TCR into HLA B27 transgenic mice, we have obtained a functional TCR transgenic model, GRb, dependent on HLA B27 for response. Surprisingly, HLA B27 supported CD4+ as well as CD8+ T cell responses in vivo and in vitro. Further, HLA B27-restricted CD4+ T cells were capable of differentiation into a range of Th1 and Th2 T cell subsets with normal patterns of cytokine expression. The transgenic T cells were also able to enhance clearance of recombinant vaccinia virus containing influenza nucleoprotein in vivo. This is the first description of a human HLA class I-restricted TCR transgenic line. The existence of CD4+ MHC class I-restricted T cells has significant implications for immune regulation in autoimmunity and, in particular, in HLA B27-associated arthritis. We believe that this model provides a novel system for the study of unusual T cell behavior in vivo.

Original publication

DOI

10.4049/jimmunol.172.1.155

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

01/2004

Volume

172

Pages

155 - 161

Addresses

Edward Jenner Institute for Vaccine Research, Compton, Nr. Newbury, Berkshire RG 20 7NN, United Kingdom.

Keywords

CD4-Positive T-Lymphocytes, Th1 Cells, Th2 Cells, CD8-Positive T-Lymphocytes, Cells, Cultured, Animals, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, Humans, Mice, Influenza A virus, Peptide Fragments, RNA-Binding Proteins, Receptors, Antigen, T-Cell, alpha-beta, Nucleoproteins, Viral Core Proteins, HLA-B27 Antigen, Cytokines, Lymphocyte Depletion, Cell Differentiation, Transgenes, Female, Interferon-gamma