Human T-Cell Lymphoma With Suppressor Effects on the Mixed Lymphocyte Reaction (MLR). II. Functional In Vitro Lymphocyte Analysis

Abstract

AbstractThe results of lymphocyte functional studies performed with the peripheral blood mononuclear cells (MNCs) of patient Wa with a non-Sezary T-cell leukemia are described. The aggressive clinical course and the distinctive histologic, cytochemical, and cytogenetic features of this T-cell lymphoproliferative disorder are detailed in an accompanying report. Immunologic marker analysis revealed that 76% of the Wa MNC fraction formed rosettes with sheep erythrocytes (E-rosettes), and on histologic examination, 95% of the E-rosettes contained neoplastic lymphocytes; 10% of the MNCs formed EAC rosettes; and 13% showed SIg positivity by immunofluorescence. In vitro mitogenic responses of Wa cells measured by 3H-thymidine incorporation were extremely low, and responses to Candida and streptococcal antigens were absent. Although a normal percentage of B cells was evident in the Wa MNC fraction, no Ig synthesis occurred in either pokeweed mitogen (PWM) stimulated or unstimulated cultures. In coculture experiments with control MNCs from two normal individuals, the Wa cells exhibited no suppressor or helper effects on the normal PWM-stimulated Ig synthesis. Importantly however, the Wa cells demonstrated suppressor effects on the normal mixed lymphocyte reaction (MLR) occurring between populations of allogeneic MNCs from two normal donors. The degree of MLR suppression increased with the presence of greater numbers of Wa cells, suggesting a dose-response relationship in these three-way MLRs. Control three-way MLRs that included two normal allogeneic lymphoid populations and other neoplastic T-cell suspensions, unrelated to Wa cells, did not show any MLR suppressor effects. Unlike the Con-A-induced MLR suppression mediated by a subset of normal T suppressor cells, the Wa suppression did not require preincubation with mitogen for the expression of this MLR suppressor activity. The absence of detectable suppressor effects by Wa cells on the proliferative responses of normal lymphocytes to Con-A and in the Ig synthesis of normal MNCs suggested that the Wa MLR suppression was a specific immune activity of the neoplastic cells rather than a nonspecific toxic effect. These data demonstrating MLR suppressor activity without suppressor effects on normal PWM-stimulated Ig synthesis have described a selective suppressor capacity possessed by the Wa cells and emphasize the usefulness of employing multiple assay systems in testing neoplastic T cells for putative T- and B-cell effector functions. Moreover, the results of this combined analysis of histology, cytochemistry, cytogenetics, and immune activity of these neoplastic T cells should provide a basis for future comparisons of other T-cell lymphoproliferative disorders with definable lymphocyte function.