Preferential production of interferon-gamma by CD4+ T cells expressing the homing receptor integrin alpha4/beta7.
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 alpha4/beta7 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. alpha4/ beta7high CD4+ T cells were more likely to produce the Th1 cytokine interferon-gamma (IFN-gamma) than were alpha4/beta7- CD4+ T cells in all six subjects studied. In contrast, production of the Th2 cytokine interleukin-4 (IL-4) was similar on alpha4/ beta7high and alpha4/beta7- CD4+ T cells. In addition, we found that human CD4+ CD45RA- T cells that adhered to the alpha4/beta7 ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produce IFN-gamma than did non-adherent cells, suggesting that the association between alpha4/beta7 expression and IFN-gamma production has functional significance. These results suggested that primary activation under Th1-promoting conditions might favour expression of alpha4/beta7. We directly examined this possibility, and found that naïve murine CD4+ T cells activated under Th1-promoting conditions expressed higher levels of alpha4/beta7 compared to cells activated under Th2-promoting conditions. The association between alpha4/beta7 expression and IFN-gamma 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.
Abramson
O
O
Lung Biology Center, Division of Pediatric Gastroenterology, and Program in Immunology, University of California San Francisco, San Francisco, CA, USA.
Qiu
S
S
Erle
D J
DJ
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007136:Immunoglobulins; D016023:Integrins; D008024:Ligands; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C071777:integrin alpha4beta7; D007371:Interferon-gamma