DIFFERENTIAL DEPENDENCE OF TH-0, TH-1 AND TH-2 CD4-CELLS ON COSTIMULATORY ACTIVITY PROVIDED BY THE ACCESSORY MOLECULE LFA-1( T)

Background The adhesion molecule LFA-1 contributes to the activation r esponse of peripheral blood human CD4+ T cells. Less is known of its c ontribution to stimulation of long-term CD4+ T cell lines and clones o r of its potential to co-stimulate CD4+ T cells of different functiona l phenotype. Objective This study was therefore performed to investiga te 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-linki ng antibodies to CD11a or CD18 with anti-CD3 antibodies to plastic and then measuring the proliferative response of CD4+ T cells to these an tibodies. Results A house duct mite allergen-specific CD4+ T cell line (TH-2) demonstrated much greater dependence on both CD11a and CD18 th an a mycobacterial antigen-specific CD4+ T cell line (TH-1). Go-stimul atory activity through LFA-1 was also provided to a house dust mite-sp ecific CD4+ T cell clone (DE-9; TH-2) but not to an influenza haemaggl utinin-specific CD4+ T cell clone (HA1 . 7; TH-0). In contrast, solubl e antibodies to GD18 inhibited proliferative responses of both DE-9 an d 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 modulat ed the phenotypic expression of LFA-1 and ICAM-1 on both HA1 . 7 and D E-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 gr eater requirement for the co-stimulatory activity of LFA-1 than CD4+ T cells of TH-0 or TH-1 phenotypes.