Effector and memory CD8+ T cells can be generated in response to alloantigen independently of CD4+ T cell help.
There is now considerable evidence suggesting that CD8(+) T cells are able to generate effector but not functional memory T cells following pathogenic infections in the absence of CD4(+) T cells. We show that following transplantation of allogeneic skin, in the absence of CD4(+) T cells, CD8(+) T cells become activated, proliferate, and expand exclusively in the draining lymph nodes and are able to infiltrate and reject skin allografts. CD44(+)CD8(+) T cells isolated 100 days after transplantation rapidly produce IFN-gamma following restimulation with alloantigen in vitro. In vivo CD44(+)CD8(+) T cells rejected donor-type skin allografts more rapidly than naive CD8(+) T cells demonstrating the ability of these putative memory T cells to mount an effective recall response in vivo. These data form the first direct demonstration that CD8(+) T cells are able to generate memory as well as effector cells in response to alloantigen during rejection in the complete absence of CD4(+) T cells. These data have important implications for the design of therapies to combat rejection and serve to reinforce the view that CD8(+) T cell responses to allografts require manipulation in addition to CD4(+) T cell responses to completely prevent the rejection of foreign organ transplants.
Jones
Nick D
ND
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, UK.
Carvalho-Gaspar
Manuela
M
Luo
Shiqiao
S
Brook
Matthew O
MO
Martin
Laurent
L
Wood
Kathryn J
KJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous
D007519:Isoantigens; D007371:Interferon-gamma