Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice.
OBJECTIVE
To determine whether cytotoxic T cells of the direct alloreactive type are activated and responsible for early, acute failure of orthotopic corneal allografts observed in eyes of C57BL/6 but not of BALB/c mice.


METHODS
Corneas from BALB/c and BALB.B mice were placed orthotopically in eyes of C57BL/6 and beta-2 microglobulin knockout mice (deficient in CD8(+) cytotoxic T cells). Graft fates were assessed clinically, and the T lymphocytes of recipients were assayed for the capacity to lyse target cells bearing donor major (MHC) and/or minor histocompatibility (minor H) antigens (direct and indirect pathways, respectively). RESULTS. Similar to BALB/c recipients, C57BL/6 mice with rejected cornea allografts acquired donor minor H-specific T cells. Unlike BALB/c recipients, C57BL/6 mice-both rejectors and acceptors-acquired donor MHC-specific T cells. beta-2 Microglobulin knockout mice showed rejection of corneal allografts in a manner indistinguishable from C57BL/6 mice, including early, acute rejection, yet T cells from beta-2 microglobulin knockout recipients of corneal allografts displayed no cytotoxic T cells specific for either donor MHC or minor H alloantigens.


CONCLUSIONS
Although C57BL/6 mice acquired donor MHC-specific cytotoxic T cells (direct alloreactive cells), neither these cells nor donor minor H-specific cytotoxic T cells (indirect alloreactive cells) play any essential role in corneal allograft rejection, including the early acute failure uniquely observed in C57BL/6 eyes.
Yamada
J
J
Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114-2500, USA.
Ksander
B R
BR
Streilein
J W
JW
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016510:Corneal Neovascularization / Q000601:surgery; D016039:Corneal Transplantation / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014184:Transplantation, Homologous