Differences in sensitivity to melphalan between Con A-activated and nonactivated human T-cell subsets

In vitro treatment with melphalan (l-PAM, l-phenylalanine mustard), 2 μg 2 × 10⁶ cells, significantly decreased the total number of E-rosette-positive (E⁺) T lymphocytes from peripheral blood (PBL) of healthy human donors as well as those of the OKT₄ (precursor suppressor/helper/inducer T cells) and OKT₁₇ populations (suppressor cells within the OKT₄ subset). The OKT₈ population (cytotoxic/mature suppressor cells) was not affected by a similar l-PAM treatment. The sensitivity of concanavalin A (Con A)-activated E⁺ T-cell populations to subsequent l-PAM treatment in vitro was different from that of Con A-untreated T cells: Thus, l-PAM treatment did not affect the expression of OKT₃ and OKT₄ antigens, increased the percentage of OKT₁₇ cells, and inhibited the experssion of OKT₈ antigen. Depletion of OKT₈ from Con A-activated E⁺ T cells (OKT₄⁺-OKT₈^--OKT₁₇⁺) did not affect their suppressive activity on PHA stimulation in l-PAM-treated as well as untreated cells. Further depletion of OKT₁₇⁺ cells from the OKT₄⁺-OKT₈^--OKT₁₇⁺ subset (OKT₄⁺-OKT₈^--OKT₁₇^-) abolished the suppressive effect on PHA stimulation. Suppressive activity of the OKT₄⁺-OKT₈^--OKT₁₇^- subset was again evident after treatment of this population with l-PAM. The results obtained indicate that the sensitivity to l-PAM treatment of various T-cell phenotypes is changed by Con A activation and that after depletion of specific T suppressor cells l-PAM seems to affect the immunoregulatory circuit within the Con A-activated OKT₄ subset.