Regulation of IFN-gamma signaling is essential for the cytotoxic activity of CD8(+) T cells.
Previous studies have demonstrated that, as naive murine CD4(+) cells differentiate into Th1 cells, they lose expression of the second chain of IFN-gammaR (IFN-gammaR2). Hence, the IFN-gamma-producing subset of Th cells is unresponsive to IFN-gamma. Analysis of IFN-gamma-producing CD8(+) T cells demonstrates that, like Th1 cells, these cells do not express IFN-gammaR2. To define the importance of IFN-gamma signaling for the development of functional CD8(+) T cells, mice either lacking IFN-gammaR2 or overexpressing this protein were examined. While CD8(+) T cell development and function appear normal in IFN-gammaR2(-/-) mice, CD8(+) T cell function in IFN-gammaR2 transgenic is altered. IFN-gammaR2 transgenic CD8(+) T cells are unable to lyse target cells in vitro. However, these cells produce Fas ligand, perforin, and granzyme B, the effector molecules required for killing. Interestingly, TG CD8(+) T cells proliferate normally and produce cytokines, such as IFN-gamma in response to antigenic stimulation. Therefore, although IFN-gamma signaling is not required for the generation of normal cytotoxic T cells, constitutive IFN-gamma signaling can selectively impair the cytotoxic function of CD8(+) T cells.
Tau
G Z
GZ
Integrated Program in Cell, Molecular, and Biophysical Studies, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cowan
S N
SN
Weisburg
J
J
Braunstein
N S
NS
Rothman
P B
PB
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D016207:Cytokines; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor