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 immu nity against respiratory virus infections, the underlying mechanisms are po orly understood. For example, although phenotypically distinct populations of memory CD4(+) T cells have been identified in different secondary lympho id tissues, it is not known which subpopulations mediate protective cellula r immunity. In this report, we demonstrate that virus-specific CD4(+) T cel ls 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 i nterferon gamma after a 5-h restimulation in vitro. Furthermore, intratrach eal adoptive transfer of lung memory cells into beta (2)m-deficient mice de monstrated that lung-resident virus-specific CD4(+) T cells mediated a subs tantial degree of protection against secondary virus infection. Taken toget her, these data demonstrate that activated memory CD4(+) T cells persisting at mucosal sites play a critical role in mediating protective cellular imm unity.