Lymphocyte Functions

Abstract

We have previously found that a monoclonal antibody completely blocked human cultured T cells’ (CTC) proliferative response to IL-2 and was also able to block absorption of IL-2 by lectin-stimulated blasts or to modulate the receptor (Bonnard et al., Transplant. Proc. in press). This monoclonal, anti-TAC, had been raised by injection of CTC for a different purpose (Uchiyama et al., J. Immunol. 126, 1393, 1980). Further study of the IL-2-receptor blockade was done by lectin-stimulation of fresh human PBL, with or without the addition of dexamethasone, followed by either ³H-thymidine incorporation or acridine orange staining of RNA, and flow-cytometry. In this system, we have previously shown that IL-2 is required to convert G_1a (middle RNA content) into G_1b cells (high RNA content) (Kristensen et al., Cell Immunol. in press). Dexamethasone-treated, lectin-stimulated, fresh PBL had impaired IL-2 production and proliferation, but their IL-2-receptors were functional, as assessed by their normal G_1a to G_1b shift and proliferation with added IL-2. The normal G_1a to G_1b transition and the proliferation was blocked by the anti-TAC (10⁻⁴ to 10⁻⁶ dilution of ascites). In contrast, fresh PBL without dexamethasone treatment, i.e. which produced IL-2 normally, were unaffected by even high concentration of anti-TAC (10^−2.5). This suggests that an important subset of T cells (helper T cells) were able to produce IL-2 and used it directly from a cytoplasmic pool. Thus membrane associated IL-2-receptors may not play a direct role in the mitogenic effect of IL-2, and anti-TAC could possibly be useful in selecting for the continued growth of helper T cell clones.