Cutting edge: Rapamycin augments pathogen-specific but not graft-reactive CD8+ T cell responses.
Recent evidence demonstrating that exposure to rapamycin during viral infection increased the quantity and quality of Ag-specific T cells poses an intriguing paradox, because rapamycin is used in transplantation to dampen, rather than enhance, donor-reactive T cell responses. In this report, we compared the effects of rapamycin on the Ag-specific T cell response to a bacterial infection versus a transplant. Using a transgenic system in which the Ag and the responding T cell population were identical in both cases, we observed that treatment with rapamycin augmented the Ag-specific T cell response to a pathogen, whereas it failed to do so when the Ag was presented in the context of a transplant. These results suggest that the environment in which an Ag is presented alters the influence of rapamycin on Ag-specific T cell expansion and highlights a fundamental difference between Ag presented by an infectious agent as compared with an allograft.
Ferrer
Ivana R
IR
Emory Transplant Center, Emory University, Atlanta, GA 30322, USA.
Wagener
Maylene E
ME
Robertson
Jennifer M
JM
Turner
Alexa P
AP
Araki
Koichi
K
Ahmed
Rafi
R
Kirk
Allan D
AD
Larsen
Christian P
CP
Ford
Mandy L
ML
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020123:Sirolimus / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
D007166:Immunosuppressive Agents; D019041:L-Selectin; D007371:Interferon-gamma; D020123:Sirolimus