Role of CD11a/CD18-CD54 interactions in suppression of human B cell responsiveness by CD4+ suppressor T cells.
The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in the suppression of human B cell function by immobilized anti-CD3-activated CD4+ T cells was examined by studying the effects of mAb to these determinants. The suppressive activity was assessed by the effects of CD4+ T cells without mitomycin C treatment activated by immobilized anti-CD3 for 72 hr on the differentiation into Ig-secreting cells of B cells activated for 72 hr with immobilized anti-CD3-stimulated CD4+ T cells that had been treated with mitomycin C (T4 mito). Suppression was not observed when activated CD4+ T cells and B cells were separated by filter membranes, indicating that the suppression requires the direct interactions between anti-CD3-activated CD4+ T cells and activated B cells. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) reversed the suppression of B cell function by suppressor CD4+ T cells significantly. Reversal of suppression of B cell function was most marked when activated B cells were treated with mAb to ICAM-1 and suppressor CD4+ T cells were treated with mAb to LFA-1, but not vice versa. Studies using fluorescence-activated cell sorter revealed marked increase of expression of ICAM-1 on B cells after 72 hr of activation with immobilized anti-CD3-stimulated T4 mito. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the suppressive activity of anti-CD3-activated CD4+ T cells to B cells. Moreover, the data are consistent with a model of T-cell-mediated B cell suppression in which interactions between LFA-1 on suppressor T cells and ICAM-1 on activated B cells play a central role in the suppression of B cell function.
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
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Hirohata
D000328:Adult; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1