The effect of TGF-β1 on adhesion molecule and chemokine receptor expression on naive T-cells

Abstract

Rationale T-cell tissue-invasion is a complex interaction between adhesion molecules, cytokines, chemokines and their receptors. TGF-β1 is well known for its immunomodulation. In this study we investigated its effect on the expression of adhesion molecules and chemokine receptors on naive CD4+ vs. CD8+ T-cells. Methods Naive T-cells were isolated from human cord-blood by negative selection (n=5). Expression of the adhesion molecules L-selectin, CLA, integrin-α E and -β 7 and CXCR3 and CCR4 was evaluated by flowcytometry, before/after 96 hours of anti-CD3 stimulation (10μg/ml) with/without TGF-β1 (10ng/ml). Results TGF-β1 increased the expression of α E integrin on both CD4+ and CD8+ T-cells (p<0,02). Majority (81%) of naive T-cells were β 7+, whereas activation significantly decreased its expression (p<0,01). Since α E and β 7 integrins compose an active unit, surprisingly much higher proportion of T-cells were α E+ compared to β 7+. Activation through the TCR significantly decreased the expression of CCR4 on both CD4+ and CD8+ T-cells, (p<0,05). However, TGF-β1 induced the expression of CCR4+ on CD8+, but not CD4+ T-cells (p<0,05). Finally, evaluating the, TGF-β1 significantly downregulated the CCR4 and CXCR3 expression on α E+ T-cells (p<0,02). Conclusions These results indicate that TGF-β1 may differently regulate the expression of α E vs β 7 integrins on both CD4+ and CD8+ naive T-cells. In addition, T-cell sensitivity towards TGF-β1 induced regulation of chemokine receptor expression is driven in part by its phenotype and the strength of the TCR-stimulation. Such TGF-β1 induced immune-modulation may have important applications in the treatment of site-specific T-cell driven inflammatory diseases.