Impaired lymphokine secretion in anergic CD4+ T cells leads to defective help for B cell growth and differentiation.

The ability of anergic helper T cells to interact with resting B cells was examined in vitro. B cell growth and differentiation in cocultures were found to be dependent on the expression of CD40 ligand (CD40L) on the cloned T cells, and the expression of this molecule was only marginally blocked by the induction of anergy. In contrast, secretion of IL-3, IL-4, IL-5, and IL-6 within the cocultures was found to be significantly reduced following the induction of anergy, and this correlated with the development of a 3- to 10-fold decrease in the ability of the T cells to induce B cell proliferation and IgG secretion. In contrast to the B cells, the activation of the T cells in these cocultures did not result in proliferation; thus, the effects of T cell anergy observed on the B cell responses were independent of an ability of clonal anergy to block T cell clonal expansion. In one T cell clone (E6), lymphokine production was reduced in part because of an increased propensity to undergo apoptosis; nevertheless, two other clones (A.E7 and 16B.2) showed no reduced viability after anergy induction. Finally, the addition of rIL-2 to the anergic T cells significantly improved their helper activity relative to control cells; this was associated with a partial reversal of the IL-3, - 4, and -5 production defects. Therefore, clonal anergy can interfere with the delivery of helper lymphokines by T cells, resulting in a decreased capacity to stimulate the growth and differentiation of B cells.