Implication for the CD94/NKG2A-Qa-1 system in the generation and function of ocular-induced splenic CD8+ regulatory T cells.
The injection of antigen into the anterior chamber (AC) induces the production of antigen-specific splenic CD8+ regulatory T cells (Tregs) /suppressor T cells that perform the local suppression of delayed-type hypersensitivity (DTH) responses. Because CD94/NKG2A-Qa-1-dependent interactions have been implicated in CD8+ Treg-mediated immune suppression and DBA/2J mice are deficient in CD94/NKG2R, we have utilized these mice to test the hypothesis that the CD94/NKG2A-Qa-1 system is essential to the induction and immunosuppressive function of CD8+ Tregs in anterior chamber-associated immune deviation (ACAID). We show that: (i) neither ACAID-mediated suppression of DTH to ovalbumin nor splenic Tregs/suppressor T cells was induced in DBA/2J mice that received an injection of antigen into the AC; (ii) splenic CD8+ Tregs from ACAID-induced DBA/2NCr mice suppressed the initiation of DTH when transferred to DBA/2J mice; (iii) following injection of antigen into the AC, intravenous administration of splenocytes or Peripheral Blood Mononuclear Cells (PBMC) isolated from DBA/2NCr but not from DBA/2J mice transferred suppression of DTH to DBA/2NCr mice; (iv) antibodies to CD94/NKG2A reduced the ACAID CD8+ T cell-mediated suppression of DTH and (v) The deficiency of such immune regulation in DBA/2J mice also correlated with a decreased number of Qa-1(b+) B cells, F4/80+ cells, a deficient number of CD94/NKG2AR and Qa-1 tetramer binding by CD8+ T cells. These results demonstrate that defective ACAID in DBA/2J mice involves multiple regulatory lesions resulting in a lack of induction of a CD8+ Treg response and possibly defective CD94/NKG2A-dependent suppression of peripheral cell-mediated immunity.
Chattopadhyay
Subhasis
S
Department of Immunology, Connecticut Lions Vascular Eye Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
O'Rourke
James
J
Cone
Robert E
RE
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000941:Antigens; D015395:Histocompatibility Antigens Class I; C527057:Klrc1 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell