Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. I. Proliferation of two distinct T-cell subsets

Abstract

In patients with carcinomatous pleural effusions blood T lymphocytes proliferated in vitro in response to autologous, freshly isolated effusion tumor cells in the autologous mixed lymphocyte-tumor culture (AMLTC) and to autologous blood non-T cells in the autologous mixed lymphocyte culture (AMLC). Treatment of the stimulator cells with the anti-HLA-DR monoclonal antibody (MAb) abrogated the stimulatory capacity in AMLC, but not in AMLTC. A subset of T cells that formed rosettes with autologous erythrocytes showed proliferative response to autologous non-malignant cells, whereas this subset did not respond to autologous tumor cells. Non-adherent lymphocytes were fractionated by centrifugation on discontinuous Percoll density gradients. Medium-sized T lymphocytes were excellent responders in AMLC, but were weak responders in AMLTC. Small T lymphocytes proliferated preferentially in AMLTC, but responded poorly in AMLC. Large granular lymphocytes (LGL) did not proliferate in mixed cultures of either type. Instead, LGL suppressed the T-cell proliferation in AMLTC. The same suppressor LGL, however, had no inhibitory effect on AMLC. Elimination of the CD4 subset reduced or abolished proliferative response in AMLC in all cases, whereas it was ineffective in diminishing the reaction in 6 of 8 AMLTC. In contrast, removal of the CD8 subset decreased or eliminated T-cell proliferation in 4 of 8 AMLTC, but in none of the AMLC. These results indicate that the autoreactive T lymphocytes detectable in response to tumor cells and non-malignant non-T cells differ in several characteristics. Thus, the reaction in the AMLTC is not due to contaminating non-malignant cells in the stimulator population and may be a tumor-induced proliferative response.