Expression of mucosal homing receptor alpha4beta7 by circulating CD4+ cells with memory for intestinal rotavirus.
The integrin alpha4beta7 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 alpha4beta7(hi) and alpha4beta7- subsets of circulating memory phenotype (CD45RA-) CD4+ T cells to proliferate in response to rotavirus, a ubiquitous intestinal pathogen. alpha4beta7(hi) memory (CD45RA-) CD4+ T cells displayed much greater reactivity to rotavirus than alpha4beta7- memory or naive (CD45RA+) CD4+ T cells. In contrast, alpha4beta7- 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 alpha4beta7+ 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 alpha4beta7 helps target and segregate intestinal versus systemic immune response.
Rott
L S
LS
Department of Pathology and the Digestive Disease Center, Stanford University, Stanford, California 94305, USA. lrott@cmgm.stanford.edu
Rosé
J R
JR
Bass
D
D
Williams
M B
MB
Greenberg
H B
HB
Butcher
E C
EC
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D006801:Humans; D007156:Immunologic Memory; D016023:Integrins / Q000502:physiology*; D007422:Intestines / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation; D051379:Mice; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D012401:Rotavirus / Q000276:immunology*
D016023:Integrins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7