Preferential production of interferon-gamma by CD4(+) T cells expressing the homing receptor integrin alpha(4)/beta(7)

Recent studies indicate that T helper type 1 (Th1) and 2 (Th2) lymphocytes differ in their expression of molecules that control T-cell migration, incl uding adhesion molecules and chemokine receptors. We investigated the relat ionship between cytokine production and expression of the homing receptor i ntegrin alpha (4)/beta (7) on T cells. We began by analysing cytokine produ ction by human CD4(+) CD45RA(-) memory/effector T cells following brief (4 hr) stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. a lpha (4)/beta (high)(7) CD4(+) T cells were more likely to produce the Th1 cytokine interferon-gamma (IFN-gamma) than were alpha (4)/beta (-)(7) CD4() T cells in all six subjects studied. In contrast, production of the Th2 c ytokine interleukin-4 (IL-4) was similar on alpha (4)/beta (high)(7) and al pha (4)/ beta (-)(7) CD4(+) T cells. In addition, we found that human CD4() CD45RA- T cells that adhered to the alpha (4)/beta (7) ligand mucosal add ressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produc e IFN-gamma than did non-adherent cells, suggesting that the association be tween alpha (4)/beta (7) expression and IFN-gamma production has functional significance. These results suggested that primary activation under Th1-pr omoting conditions might favour expression of alpha (4)/beta (7) we directl y examined this possibility, and found that naive murine CD4+ T cells activ ated under Th1-promoting conditions expressed higher levels of alpha (4)/be ta (7) compared to cells activated under Th2-promoting conditions. The asso ciation between alpha (4)/beta (7) expression and IFN-gamma production by C D4(+) T cells may help to determine the cytokine balance when MAdCAM-1 is e xpressed at sites of inflammation in the intestine or elsewhere.