Bidirectional Modulation of Human B Cell Stimulation by Activated T Cells

Although human T cells have been shown to exert effects of both help and suppression on B cells, the precise sequelae for these different effects have not yet been delineated. The present study therefore examined in detail the Functions of human peripheral blood T cells activated for various periods by immobilized anti-CD3 to modulate B cell responses. CD4+ (CD45RA+ or CD45RA-) or CD8+ (CD45RA+ or CD45RA-) T cell subsets were cultured in wells with immobilized anti-CD3 for as long as 20 days. At various periods of time, these activated T cells were harvested and cocultured with either fresh resting B cells or preactivated B cells. CD4+ and CD8+ T cells, irrespective of their expression of the CD45RA molecule, were able to stimulate resting B cells to express transferrin receptor (CD71) and IL-2 receptor (CD25) up to 17 days after activation with immobilized anti-CD3, although CD8+ but not CD4+ T cell subsets appeared to become less potent in stimulating resting B cells after 17 days of activation. By contrast, these CD4+ and CD8+ T cell subsets activated by immobilized anti-CD3 suppressed the maturation of the B cells preactivated with anti-CD3-stimulated CD4+ T cells, at the same time as when they provided help for resting B cells. The suppression, but not the help, was abrogated by treatment of the T cells with mitomycin C up to 13 days after activation. The suppression was not abrogated by addition of exogenous IL-2, irrespective of the length of stimulation of suppressor-effector T cells. These results indicate that human activated T cells can provide help and suppression simultaneously, irrespective of their phenotypes. Moreover, the data suggest that the state of activation of B cells might be important in determining the functions of the activated T cells.