LFA-1 contributes to signal I of T-cell activation and to the production of T(h)1 cytokines.

Varga G, Nippe N, Balkow S, Peters T, Wild MK, Seeliger S, Beissert S, Krummen M, Roth J, Sunderkötter C, Grabbe S

Abstract

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the proliferation of CD18(-/-) T cells was significantly reduced, whereas cytokine production remained impaired. The diminished proliferative capacity of CD18(-/-) T cells could be fully compensated for by additional triggering of the T-cell receptor, but not by additional stimulation through the costimulatory molecule, CD28. Thus, ligation of LFA-1 on T cells participates in regulation of Th1 cytokines in vivo. In addition, LFA-1 primarily exerts an effect as an enhancer of TCR signalling and does not facilitate classical costimulation.