CD8+ regulatory T cells generated by neonatal recognition of peripheral self-antigen.
In comparison with CD4+ regulatory T cells, the generation and function of immunomodulatory CD8+T cells is less well defined. Here we describe the existence of regulatory anti-Kb-specific CD8+ T cells that are rendered tolerant during neonatal life via antigen contact exclusively on keratinocytes. These regulatory T cells maintain tolerance during adulthood as they prevent Kb-specific graft rejection by naïve CD8+ T cells. Third-party immune responses remain unaffected. Up-regulation of TGF-beta1 and granzyme B in the regulatory CD8+ T cell population suggests the involvement of these molecules in common suppressive pathways shared with CD4+ regulatory T cells. In summary, CD8+ regulatory T cells can be induced extrathymically through antigen contact on neonatally accessible parenchymal cells and maintain tolerance throughout adult life.
Reibke
Roland
R
*Division of Molecular Immunology (D050), German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Garbi
Natalio
N
Ganss
Ruth
R
Hämmerling
Günter J
GJ
Arnold
Bernd
B
Oelert
Thilo
T
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens