Salvatore Venuta

Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2.

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies OKT3 and Pan T2, to induce proliferation and interleukin 2 (IL2) production in peripheral blood lymphocytes (PBL) from 21 homosexual patients: 12 with Kaposis sarcoma (KS), 4 with reactive lymphadenopathy, and 5 with opportunistic infections. All patients with KS and opportunistic infections had significantly lower mitogen-stimulated DNA synthesis, as compared to the controls, irrespective of the mitogen used (P<0.01). The patients with lymphadenopathy exhibited significantly lower responses only in the OKT3 assay as compared to normals (P=0.009). The production of endogenous IL2 was significantly lower in PBL cultures from patients with KS and with opportunistic infections, irrespective of the mitogen used, as compared to healthy male controls, and also significantly lower in the Pan T2-stimulated cultures from patients with lymphadenopathy. The addition of highly purified IL2 was able to restore partially lymphocyte proliferationin vitro in the presence of these mitogens in all patients. Our studies demonstrate (1) that male homosexuals even without clinical manifestations of immunodeficiency frequently exhibit a proliferative T-cell defect when anti-T-cell monoclonal antibodies rather than PHA are used as mitogens, (2) that this proliferative defect is associated with defective IL2 production, and (3) that this defect is at least in part correctablein vitro by highly purified IL2.

Interleukin-2 correction of defectivein vitro T-cell mitogenesis in patients with common varied immunodeficiency

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies, OKT3 and Pan T2, to induce interleukin-2 (IL2) production and proliferation in peripheral blood lymphocytes (PBL) from 14 patients with combined varied immunodeficiency (CVI). The median values of endogenous IL2 produced by mitogen-stimulated PBL was significantly lower in patients than controls irrespective of the mitogen used. The patients, taken as a group, had a significantly decreasedin vitro PBL response to mitogen stimulation when compared to controls. With the addition of a highly purified human IL2 preparation, the proliferative response in the majority of patients was significantly improved with all mitogens. Three patient groups could be distinguished: Group A (3/14) had full restoration of proliferative response with the addition of IL2, Group B (5/14) had partial restoration, and Group C (6/14) had no significant response. The monoclonal antibody, Pan T2, recognized a T-cell proliferative defect in 5 of 14 patients which neither PHA nor OKT3 recognized. This was not significantly corrected by the addition of IL2. This T-cell proliferative defect correlated with the lack of B-cell proliferation and immunoglobulin production in response to B-cell mitogens in three-fourths of the patients assayed. These data show that CVI patients are a heterogeneous group but have in common a decreasedin vitro production of IL2 resulting in a proliferative defect which is correctable at least in part,in vitro, in the majority by the addition of purified IL2.