Protection from respiratory virus infections can be mediated by antigen-specific CD4(+) T cells that persist in the lungs.
Although CD4(+) T cells have been shown to mediate protective cellular immunity against respiratory virus infections, the underlying mechanisms are poorly understood. For example, although phenotypically distinct populations of memory CD4(+) T cells have been identified in different secondary lymphoid tissues, it is not known which subpopulations mediate protective cellular immunity. In this report, we demonstrate that virus-specific CD4(+) T cells persist in the lung tissues and airways for several months after Sendai virus infection of C57BL/6 mice. A large proportion of these cells possess a highly activated phenotype (CD44(hi), CD62L(lo), CD43(hi), and CD25(hi)) and express immediate effector function as indicated by the production of interferon gamma after a 5-h restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung memory cells into beta2m-deficient mice demonstrated that lung-resident virus-specific CD4(+) T cells mediated a substantial degree of protection against secondary virus infection. Taken together, these data demonstrate that activated memory CD4(+) T cells persisting at mucosal sites play a critical role in mediating protective cellular immunity.
Hogan
R J
RJ
Trudeau Institute, Saranac Lake, New York 12983, USA.
Zhong
W
W
Usherwood
E J
EJ
Cookenham
T
T
Roberts
A D
AD
Woodland
D L
DL
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010253:Respirovirus Infections / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma