Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.
BACKGROUND
In contrast to intestinal CD4(+) regulatory T cells (T(regs)), the generation and function of immunomodulatory intestinal CD8(+) T cells is less well defined. To dissect the immunologic mechanisms of CD8(+) T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cell-receptor specific for HA was studied.


RESULTS
HA-specific CD8(+) T cells were isolated from gut-associated tissues and phenotypically and functionally characterized for the expression of Foxp3(+) and their suppressive capacity. We demonstrate that intestinal HA expression led to peripheral induction of HA-specific CD8(+)Foxp3(+) T cells. Antigen-experienced CD8(+) T cells in this transgenic mouse model suppressed the proliferation of CD8(+) and CD4(+) T cells in vitro. Gene expression analysis of suppressive HA-specific CD8(+) T cells revealed a specific up-regulation of CD103, Nrp1, Tnfrsf9 and Pdcd1, molecules also expressed on CD4(+) T(reg) subsets. Finally, gut-associated dendritic cells were able to induce HA-specific CD8(+)Foxp3(+) T cells.


CONCLUSIONS
We demonstrate that gut specific antigen presentation is sufficient to induce CD8(+) T(regs)in vivo which may maintain intestinal homeostasis by down-modulating effector functions of T cells.
Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Diana
D
Fleissner
Wiebke
W
Hansen
Robert
R
Geffers
Jan
J
Buer
Astrid M
AM
Westendorf
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007422:Intestines / Q000166:cytology* / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic