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

Abstract

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 Kaposi's 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 less than 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 proliferation in 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 correctable in vitro by highly purified IL2.

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.

“…Early experiments studying proliferation or IL-2 production from cells of HIV-infected patients stimulated with PHA or tetanus raised the issue of whether a qualitative defect of 1L-2 production existed in these patients (17)(18)(19)(20)(21)(22)(23)(24). The data in Table 2 (Experiment 2), show that IL-2 pro- TET 0 70 180 12 0 0 140 ND 600 PHA 600 500 515 600 250 175 410 400 TET 0 30 120 7 0 0 70 ND HIV PHA 275 375 635 500 10 60 470 200 TET 22 70 280 45 0 10 duction was often higher from PBMCs and CD4 + T cells in response to PHA in HIV + individuals compared to HIV-controls.…”

Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

“…þ cells, a vigorous (but still insufficient) cell-mediated cytotoxic (CTL) response against all major HIV proteins [1], reduced natural immunity [2], impaired proliferative responses to nonspecific mitogens, and altered cytokine production, including interferon-␥ (IFN-␥) [3][4][5][6] and interleukin-2 (IL-2) [7,8]. Immune intervention and antiretroviral treatment target different aspects of HIV infection, but the ultimate goals of HIV therapy are to induce suppression of viral replication and to enhance CD4 þ cell number and function for optimal restoration and preservation of the immune system.…”

Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome.

“…1 A, 2 A). In addition, it is possible that the abnormal presence of endogenous IFNa may be involved in the pathogenesis of some immune disturbances in AIDS patients, such as suppressed natural killer cell activities, deficient proliferative responses to mitogens, or possible feedback inhibition of lymphokine production including IL-2 and IFNy (3,8,9,13,14).…”