Preferential production of interferon-γ by CD4+ T cells expressing the homing receptor integrin α4/β7

Abstract

Recent studies indicate that T helper type 1 (Th1) and 2 (Th2) lymphocytes differ in their expression of molecules that control T-cell migration, including adhesion molecules and chemokine receptors. We investigated the relationship between cytokine production and expression of the homing receptor integrin α4/β7 on T cells. We began by analysing cytokine production by human CD4+ CD45RA- memory/effector T cells following brief (4 hr) stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. α4/βhigh7 CD4+ T cells were more likely to produce the Th1 cytokine interferon-γ (IFN-γ) than were α4/β7- CD4+ T cells in all six subjects studied. In contrast, production of the Th2 cytokine interleukin-4 (IL-4) was similar on α4/βhigh7 and α4/β7- CD4+ T cells. In addition, we found that human CD4+ CD45RA- T cells that adhered to the α4/β7 ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produce IFN-γ than did non-adherent cells, suggesting that the association between α4/β7 expression and IFN-γ production has functional significance. These results suggested that primary activation under Th1-promoting conditions might favour expression of α4/β7. We directly examined this possibility, and found that naïve murine CD4+ T cells activated under Th1-promoting conditions expressed higher levels of α4/β7 compared to cells activated under Th2-promoting conditions. The association between α4/β7 expression and IFN-γ production by CD4+ T cells may help to determine the cytokine balance when MAdCAM-1 is expressed at sites of inflammation in the intestine of elsewhere.