Differential homing commitments of antigen-specific T cells after oral or parenteral immunization in humans

Animal experiments show that lymphocytes activated in the intestine circula te through mesenteric Ij mph nodes, lymphatics, and blood, returning to the gut. Homing into intestinal lamina propria is mediated by lymphocyte surfa ce homing receptors, mainly the alpha(4)beta(7)-integrin. We studied in hum ans whether intestinal T cells entering the blood upon antigenic activation would exhibit homing commitments to the gut. Volunteers mere immunized wit h keyhole limpet hemocyanin (KLH) first orally and then parenterally or onl y parenterally, and the expression of alpha(4)beta(7) on T cells specific f or KLH or tetanus toroid was studied. Circulating T cells were depleted of alpha(4)beta(7)(+) cells by immunomagnetic selection. This depletion remove d a significant proportion of the KLH-specific cells (mean decrease in prol iferative response of 71%) in the orally immunized volunteers. No differenc e in the KLH-induced proliferation was found between the total and the alph a(4)beta(7)-depleted populations in volunteers parenterally immunized with KLH, regardless of whether a preceding mucosal priming had taken place or n ot. In both immunization groups, the depletion of alpha(4)beta(7)(+) cells had no influence on the proliferative response to tetanus toroid. We conclu de that, in contrast to T cells activated by parenteral immunization, gut-d erived T cells have preferential homing commitments to the gut. This commit ment was no longer observed after a subsequent parenteral Ag administration . Besides showing that the site of Ag encounter determines the expression o f homing receptors, the present study is the first to provide evidence for a circulation of newly activated Ag-specific intestinal T cells back to the gut in humans.