In vivo generation of pathogen-specific Th1 cells in the absence of the IFN-gamma receptor.
The precise mechanisms that govern the commitment of CD4 T cells to become Th1 or Th2 cells in vivo are incompletely understood. Recent experiments demonstrate colocalization of the IFN-gammaR chains with the TCR during activation of naive CD4 T cells, suggesting that association of these molecules may be involved in determining lineage commitment. To test the role of IFN-gamma and its receptor in the generation of Th1 Ag-specific CD4 T cells, we analyzed mice after infection with Listeria monocytogenes or lymphocytic choriomeningitis virus. In the absence of IFN-gamma, Ag-specific CD4 T cells were generated in response to both these infections. In addition, IFN-gamma-producing (Th1) Ag-specific CD4 T cells were generated in mice lacking the ligand-binding chain of the IFN-gammaR (IFN-gammaR1-/-) or the signaling chain (IFN-gammaR2-/-). There was no increase in the number of IL-4-producing Ag-specific CD4 T cells, nor was there a decrease in the expression of T-bet in the absence of functional IFN-gamma signaling, indicating that the cells were committed Th1 cells. Thus, both chains of the IFN-gammaR are dispensable for the generation of Th1 Ag-specific CD4 T cells after infection in vivo.
Haring
Jodie S
JS
Department of Microbiology, University of Iowa, Iowa City 52242, USA.
Badovinac
Vladimir P
VP
Olson
Matthew R
MR
Varga
Steven M
SM
Harty
John T
JT
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006460:Hemolysin Proteins; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D017471:Receptors, Interferon / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology*; D000096743:Interferon gamma Receptor
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007371:Interferon-gamma; D010446:Peptide Fragments; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C038705:hlyA protein, Listeria monocytogenes