Antibody-independent antiviral function of memory CD4+ T cells in vivo requires regulatory signals from CD8+ effector T cells.
Previous studies have shown that vaccine-primed CD4(+) T cells can mediate accelerated clearance of respiratory virus infection. However, the relative contributions of Ab and CD8(+) T cells, and the mechanism of viral clearance, are poorly understood. Here we show that control of a Sendai virus infection by primed CD4(+) T cells is mediated through the production of IFN-gamma and does not depend on Ab. This effect is critically dependent on CD8(+) cells for the expansion of CD4(+) T cells in the lymph nodes and the recruitment of memory CD4(+) T cells to the lungs. Passive transfer of a CD8(+) T cell supernatant into CD8(+) T cell-depleted, hemagglutinin-neuraminidase (HN)(421-436)-immune muMT mice substantially restored the virus-specific memory CD4(+) response and enhanced viral control in the lung. Together, the data demonstrate for the first time that in vivo primed CD4(+) T cells have the capacity to control a respiratory virus infection in the lung by an Ab-independent mechanism, provided that CD8(+) T cell "help" in the form of soluble factor(s) is available during the virus infection. These studies highlight the importance of synergistic interactions between CD4(+) and CD8(+) T cell subsets in the generation of optimal antiviral immunity.
Zhong
W
W
Trudeau Institute, Saranac Lake, NY 12983, USA.
Roberts
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AD
Woodland
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D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015707:HN Protein / Q000276:immunology*; D007116:Immunization, Passive; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D018108:Respirovirus / Q000276:immunology*; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015707:HN Protein; D010446:Peptide Fragments; D014765:Viral Vaccines; D007371:Interferon-gamma