Lung memory CD4 T cell subsets with different tissue retentive properties (102.1)

Abstract

Abstract Memory T cells residing in the lung can mediate protective immunity to pathogens; however, the mechanism of lung cell recruitment and retention is unknown. We have shown that antigen-specific lung memory CD4 T cells can traffic to the lung and become irreversibly retained there, whereas lymphoid memory T cells distribute widely and are not retained in tissues. However, endogenous polyclonal lung memory CD4 cells migrate to the lung and additional tissue sites. We hypothesized that the lung memory CD4 T cell population is comprised of both tissue-resident and circulating subsets. To identify these subsets we labeled CD4 cells by intravenous administration of fluorescently labeled anti-CD4 antibody and found that 25% of CD4 cells in lungs were protected from labeling and were mostly CD11ahi CD69+. Inhibiting lymphocyte circulation with FTY720 resulted in a decrease in lung naïve cells but retention of the memory cells enriched for CD11ahi CD69+ cells. We have also found that tissue-specific recruitment of lung memory cells was inhibited by pertussis toxin, suggesting the involvement of chemokine receptors. Microarray and phenotypic analysis revealed higher expression of CCR6 and CD103 by lung memory CD4 cells. Transfer of lung memory CD4 cells resulted in CCR6+ and CD103+ donor cells being enriched in the lung-recruited population. Our data suggest that the lung memory CD4 T cell population consists of a circulatory subset and a tissue-retentive subset with distinct phenotypes.