Differential dependence of TH-0, TH-1 and TH-2 CD4+ T cells on co-stimulatory activity provided by the accessory molecule LFA-1

Background. The adhesion molecule LFA-1 contributes to the activation response of peripheral blood human CD4+ T cells. Less is known of its contribution to stimulation of long-term CD4+ T cell lines and clones or of its potential to co-stimulate CD4+ T cells of different functional phenotype. Objective. This study was therefore performed to investigate co-stimulatory properties of the LFA-1 (CD11a/CD18) complex in the activation of human CD4+ T cell lines and clones of TH-0, TH-1 and TH-2 subsets. Methods. Co-stimulatory activity was measured by cross-linking antibodies to CD11a or CD18 with anti-CD3 antibodies to plastic and then measuring the proliferative response of CD4+ T cells to these antibodies. Results. A house duct mite allergen-specific CD4+ T cell line (TH-2) demonstrated much greater dependence on both CD11a and CD18 than a mycobacterial antigen-specific CD4+ T cell line (TH-1). Co-stimulatory activity through LFA-1 was also provided to a house dust mite-specific CD4+ T cell clone (DE-9; TH-2) but not to an influenza haemagglutinin-specific CD4+ T cell clone (HA1.7; TH-0). In contrast, soluble antibodies to CD18 inhibited proliferative responses of both DE-9 and HA1.7 to an immunogenic challenge of antigen and to stimulation by anti-CD3 antibodies. However, the allergen-specific T cells were more susceptible to inhibition. Signal transduction was also observed from the T-cell receptor to LFA-1. Ligation of the T-cell receptor modulated the phenotypic expression of LFA-1 and ICAM-1 on both HA1.7 and DE-9. Phenotypic modulation was observed as a result of both activation and the induction of non-responsiveness. Conclusion. These experiments indicate that CD4+ T cells of TH-2 functional phenotype may have a greater requirement for the co-stimulatory activity of LFA-1 than CD4+ T cells of TH-0 or TH-1 phenotypes.