Gammadelta T cells in anterior chamber-induced tolerance in CD8(+) CTL responses.
OBJECTIVE
Delivery of antigen to the anterior chamber (AC) of the eye induces a systemic form of tolerance, referred to as anterior chamber-associated immune deviation (ACAID). ACAID is characterized by decreases in delayed-type hypersensitivity responses and complement-fixing antibodies on subsequent challenge with an immunogenic form of the antigen. The current study was designed to test whether priming of antigen-specific CD8(+) cytotoxic T-lymphocytes (CTLs) are inhibited by injection of soluble antigen into the AC and whether gammadelta T cells play a role in the inhibition of such responses.


METHODS
Antigen was administered through the AC to normal gammadelta T-cell-deficient or reconstituted gammadelta T-cell-deficient mice. Seven days after the AC injection, the mice were primed with antigen in adjuvant and 10 days later, their spleen cells were cultured for 5 to 7 days and the CTL responses measured.


RESULTS
CTL responses were inhibited by antigen delivered through the AC in normal but not gammadelta T-cell-deficient mice. Tolerance was reconstituted in delta-chain knockout mice by the adoptive transfer of gammadelta T cells from normal mice. Moreover, spleen cells and splenic gammadelta(+) T cells, but not gammadelta(-) T cells, from mice injected with antigen through the AC inhibited development of CTL responses when cultured together with primed effector T cells.


CONCLUSIONS
These data show, for the first time, that administration of soluble antigen in the AC inhibits development of CD8(+) cytotoxic T-cell responses and that gammadelta T cells play a critical role in inhibition of CTL responses.
Xu
Yijun
Y
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Kapp
Judith A
JA
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D010047:Ovalbumin