Expression of mucosal homing receptor alpha 4 beta 7 by circulating CD4(+) cells with memory for intestinal rotavirus

The integrin alpha 4 beta 7 mediates lymphocyte binding to mucosal addressin cell adhesion molecule-1, and its expression defines lymphocytes capable of trafficking through the intestines and the intestinal lymphoid tissues, We examined the ability of discrete alpha 4 beta 7(hi) and alpha 4 beta 7(-) subsets of circulating memory phenotype (CD45RA(-)) CD4(+) T cells to proliferate in response to rotavirus, a ubiquitous intestinal pathogen. alpha 14 beta 7(hi) memory (CD45RA(-)) CD4(+) T cells displayed much greater reactivity to rotavirus than alpha 4 beta 7(-) memory or naive (CD45RA(+)) CD4(+) T cells, In contrast, alpha 4 beta 7(-) memory cells were the predominant population responsive to mumps antigen after intramuscular vaccination. Our results are consistent with the conclusion that natural rotavirus infection, an enteric pathogen, results in a specific circulating memory CD4(+) response that is largely limited to the gut-homing alpha 3 beta 7(+) subpopulation, This phenotype is not shared with memory cells elicited by intramuscular immunization (shown here) or by skin contact allergens, The results support the hypothesis that gut trafficking memory CD4(+) T cells comprise cellular memory for intestinal antigens and suggest that regulated expression of alpha 4 beta 7 helps target and segregate intestinal versus systemic immune response.