T4+ cell production of interferon gamma and the clinical spectrum of patients at risk for and with acquired immunodeficiency syndrome.

To fully characterize the relationship between the clinical manifestations of human immunodeficiency virus infection and T4+ cell defects, we determined T4+ cell number and interferon gamma (IFN-gamma) production in 238 patients. For asymptomatic homosexuals, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and patients with fully established AIDS, clinical status correlated linearly with both T4+ cell number and T4+ cell-derived (antigen-stimulated) IFN-gamma secretion. For asymptomatic homosexuals, abnormalities in T4+ cell number and IFN-gamma generation were similar irrespective of human immunodeficiency virus seropositivity. For patients with ARC, those with lymphadenopathy (LA) alone or LA plus zoster or thrombocytopenia displayed T4+ cell defects similar to those observed in asymptomatic homosexuals. Patients with ARC with LA plus constitutional symptoms and/or oral thrush, however, had fewer T4+ cells, were strikingly more deficient in IFN-gamma production, and closely resembled those with AIDS. Among patients with AIDS, certain individuals with Kaposi's sarcoma (KS) alone were sufficiently less cytopenic and less immunodeficient than patients with opportunistic infections (Ols) to suggest that the immune impairment that predisposes to KS may differ. At the time patients with KS developed Ols, however, T4+ cell number and IFN-gamma-generating capacity had declined to the remarkably low levels observed in virtually all patients with Ols alone.

T lymphocyte responses to mycobacterial antigen in AIDS patients with disseminated Mycobacterium avium-Mycobacterium intracellulare infection.

Patients with acquired immunodeficiency syndrome (AIDS) who have Mycobacterium avium-Mycobacterium intracellulare (MAI) infection typically have widely disseminated disease, often fail to respond to multi-drug chemotherapeutic regimens, and show little or no inflammatory tissue response. To determine if this clinicopathologic state correlates with in vitro lymphocyte responses to specific antigen, peripheral blood mononuclear cells from 18 patients with AIDS who had MAI bacillemia were stimulated with either particulate (heat-killed bacille Calmette Guérin [BCG]) or soluble (M intracellulare) mycobacterial antigens. In comparison to reactive cells from healthy control subjects testing positive with purified protein derivative of tuberculin (PPD) or from MAI-colonized (non-AIDS) control subjects, cells from 16 (89 percent) patients with AIDS essentially failed to show any antigen-induced proliferative activity or secretion of gamma-interferon; however, in two patients, antigen-stimulated proliferation of gamma-interferon production was modest but within the range of responses of normal healthy control subjects. Thus, although an occasional patient with AIDS can develop disseminated MAI infection despite the presence of antigen-reactive cells in vitro, most MAI-infected patients with AIDS display a striking defect in responsiveness to both particulate and soluble mycobacterial antigens. Since treatment with gamma-interferon activates the mononuclear phagocyte in vivo, these results suggest a rationale for a trial of gamma-interferon therapy in patients with AIDS who have disseminated MAI infection.