Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-gamma signaling.
Recent studies indicate that IFN-gamma may influence both the expansion and the trafficking of virus-specific CD8+ CTL, though the effects are not necessarily consistent for different models of viral and bacterial disease. Influenza A virus infection of mice deficient for IFN-gamma (IFN-gamma(-/-)) or deficient for the IFN-gamma receptor 1 (IFNGR1(-/-)) was, when compared with the wild-type (WT) B6 controls, associated with increased Ag-specific CD8+ T cell counts in the spleen and mediastinal lymph nodes. At the same time, fewer of these CTL effectors were found in the bronchoalveolar lavage population recovered from the IFN-gamma(-/-) mice. Comparable effects were observed for WT mice treated with a neutralizing IFN-gamma-specific mAb. Transfer of WT memory Thy1.1(+) CD8+ populations into Thy1.2+ B6 IFN-gamma(-/-) or IFNGR1(-/-) mice followed by intranasal virus challenge demonstrated both that IFN-gamma produced by the host was important for the regulation of Ag-specific CTL numbers and that IFN-gamma was likely to act directly on the T cells themselves. In addition, the prevalence of CTLs undergoing apoptosis in spleen was lower when measured directly ex vivo for IFN-gamma(-/-) vs WT B6 mice. The present analysis is the first comprehensive demonstration that IFN-gamma signaling can differentially regulate both Ag-specific CTL homeostasis in secondary lymphoid organs and trafficking to a site of virus-induced pathology.
Turner
Stephen J
SJ
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. sjturn@unimelb.edu.au
Olivas
Elvia
E
Gutierrez
Astrid
A
Diaz
Gabriela
G
Doherty
Peter C
PC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006706:Homeostasis; D009980:Influenza A virus; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D000096743:Interferon gamma Receptor
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007371:Interferon-gamma; D019707:Receptors, Chemokine; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor