Memory CD8+ T cells protect dendritic cells from CTL killing.
CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in sharp contrast to the effector cells (CTLs) that kill DCs in a granzyme B- and perforin-dependent mechanism, memory CD8(+) T cells enhance the ability of DCs to produce IL-12 and to induce functional Th1 and CTL responses in naive CD4(+) and CD8(+) T cell populations. Moreover, memory CD8(+) T cells that release the DC-activating factor TNF-alpha before the release of cytotoxic granules induce DC expression of an endogenous granzyme B inhibitor PI-9 and protect DCs from CTL killing with similar efficacy as CD4(+) Th cells. The currently identified DC-protective function of memory CD8(+) T cells helps to explain the phenomenon of CD8(+) T cell memory, reduced dependence of recall responses on CD4(+) T cell help, and the importance of delayed administration of booster doses of vaccines for the optimal outcome of immunization.
Watchmaker
Payal B
PB
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213-1863, USA.
Urban
Julie A
JA
Berk
Erik
E
Nakamura
Yutaro
Y
Mailliard
Robbie B
RB
Watkins
Simon C
SC
van Ham
S Marieke
SM
Kalinski
Pawel
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053804:Granzymes / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D054353:Perforin / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
D054353:Perforin; D053804:Granzymes