Cutting Edge: Virus-Specific CD4+ Memory T Cells in Nonlymphoid Tissues Express a Highly Activated Phenotype1

Recent studies have shown that CD4+ memory T cells persist in nonlymphoid organs following infections. However, the development and phenotype of these peripheral memory cells are poorly defined. In this study, multimerized MHC-Ig fusion proteins, with a covalently attached peptide sequence from the Sendai virus hemagglutinin/neuraminidase gene, have been used to identify virus-specific CD4+ T cells during Sendai virus infection and the establishment of peripheral CD4+ memory populations in the lungs. We show declining frequencies of virus-specific CD4+ T cells in the lungs over the course of ∼3 mo after infection. Like peripheral CD8+ T cells, the CD4+ have an acutely activated phenotype, suggesting that a high level of differentiation is required to reach the airways and persist as memory cells. Differences in CD25 and CD11a expression indicate that the CD4+ cells from the lung airways and parenchyma are distinct memory populations.