ABSTRACT
gammadelta T lymphocytes in the intestinal intraepithelial layer (gammadelta IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of gammadelta IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8(+) alphabeta T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8(+) alphabeta T cells must be activated to become cytotoxic effectors, gammadelta IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that gammadelta IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. gammadelta IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general.
Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/immunology , Animals , Antigen Presentation , CD8-Positive T-Lymphocytes/immunology , Cholesterol/metabolism , Cytotoxicity, Immunologic , Female , Gene Expression , Immunity, Mucosal , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Lipid Metabolism , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis , Signal Transduction , Transcription, Genetic , Yersinia pseudotuberculosis Infections/genetics , Yersinia pseudotuberculosis Infections/immunologyABSTRACT
IL-7 and IL-15 play important roles in gammadelta T cell development. These receptors transmit proliferation and/or survival signals in gammadelta T cells. In addition, the IL-7R promotes recombination and transcription in the TCR gamma locus. To clarify the role of the cytokine receptors in the development of epidermal gammadelta T cells, we introduced a Vgamma3/Vdelta1 TCR transgene, derived from Thy-1+ dendritic epidermal T cells (DETC), into IL-7Ralpha-deficient mice, and we found that they partly rescued gammadelta T cells in the adult thymus but not in the spleen. Introduction of an additional Bcl-2 transgene had a minimal effect on gammadelta T cells in the adult thymus of these mice. In contrast to the adult thymus, the introduction of the Vgamma3/Vdelta1 TCR transgene into IL-7Ralpha-/- mice completely restored Vgamma3+ T cells in the fetal thymus and DETC in the adult skin. On the contrary, the same Vgamma3/Vdelta1 TCR transgene failed to rescue DETC in the skin of IL-2Rbeta-deficient mice, even with the additional Bcl-2 transgene. These results suggest that the IL-2/IL-15R, rather than the IL-7R, plays an essential role in proliferation and survival of DETC in the fetal thymus and the skin. In contrast, the IL-7R is probably essential in the induction of V-J recombination of TCRgamma genes. Thus, this study proves that IL-7R and IL-2/IL-15R serve differential functions in epidermal gammadelta T cell development.
