Cutting edge: early IFN-gamma signaling directly enhances primary antiviral CD4+ T cell responses.
IFN-gamma drives CD4+ T cell differentiation toward the Th1 phenotype (Th1) and suppresses Th2 development. Current evidence indicates that IFN-gamma inhibits T cell proliferation and decreases T cell survival. In contrast to the above, we show here that antiviral CD4+ T cell generation after infection is reduced in the absence of IFN-gamma signals. The deficient expansion of cells was not due to perturbations in T cell sensitivity to peptide or to altered migratory patterns through nonlymphoid tissues. Instead, IFN-gamma enhanced early antiviral CD4 responses largely through direct signals into these cells. Our data challenge prevailing dogma and have implications for how the sizes of the CD8+ and CD4+ T cell responses are established.
Whitmire
Jason K
JK
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Benning
Nicola
N
Whitton
J Lindsay
JL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor