Peripheral blood of aids patients contains cells capable of providing accessory function for the natural killer cell-mediated, lysis of herpes simplex virus-infected targets despite low interferon-αproduction

We have previously demonstrated that in vitro production of interferon-α(IFN-α) in response to herpes simplex virus (HSV) by peripheral blood mononuclear cells PBMCs from patients infected with the human immunodeficiency virus (HIV-1) decreases dramatically with disease progression, with extremely low levels of IFN-αpreceding and predictive of opportunistic infections. Natural killer (NK) lysis, however, was found to decay later in disease and often was within normal limits even when IFN-αproduction was severely compromised. The NK lysis of HSV-infected fibroblasts (HSV-FS) is dependent on an HLA-DR⁺accessory cell (AC) population that shares the phenotype of the predominant IFN-α-producing cell (IPC) population. To determine whether there is a correlation between AC activity and IFN-αproduction in these patients, we tested the ability of PBMCs from AIDS patients to provide AC help to NK cells from heterologous donors. While NK cells were highly sensitive to gamma irradiation, AC activity was relatively radioresistant. Therefore, NK cells from healthy donors were depleted of HLA-DR⁺ACs and added to irradiated PBMCs from either healthy or AIDS donors to test for the function of ACs in the irradiated populations. Irradiated cells from AIDS patients were found to provide normal AC activity despite decreased IFN-αproduction in the majority of the patients. We failed to observe NK augmenting activity in supernatants of irradiated PBMCs from IFN-deficient patients that had been stimulated with HSV-FS. We conclude that IFN-αproduction and AC function are either mediated by different populations of cells or represent independently regulated functions of the same cells and that IFN-αproduction can be compromised in patients whose AC function is intact.