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

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/ 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/ 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 or elsewhere.