B7 costimulation is necessary for the activation of the lytic function in cytotoxic T lymphocyte precursors.
B7-CD28 costimulation is essential for the activation of CD4+ T helper cells, mainly by regulating IL-2 and other cytokine production. The requirement for this costimulatory pathway in the activation of CD8+ T cells, however, is still poorly understood. Here we analyzed the role of B7-CD28 costimulation in the differentiation of Ag-specific CTL precursor. We found that the activation of not only IL-2 production but also cytotoxic function in CD8 T cells requires B7 costimulation. The costimulatory signal, which cannot be replaced by exogenous IL-2, is directly implicated in the activation of the lytic machinery in CD8 T cells. Moreover, B7-CD28 costimulation appears to play a critical role in the accumulation of mRNA encoding at least one of the granzymes required for cytolytic function, granzyme B or CTLA-1. The production of IFN-gamma by CD8 T cells, however, does not appear to require costimulation.
Guerder
S
S
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Carding
S R
SR
Flavell
R A
RA
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D053804:Granzymes; D018960:Hyaluronan Receptors / Q000502:physiology; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018960:Hyaluronan Receptors; D018796:Immunoconjugates; D007376:Interleukin-2; D012333:RNA, Messenger; D000069594:Abatacept; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases