HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION ALTERS ANTIGEN-INDUCED CYTOKINE RESPONSES IN PATIENTS WITH ACTIVE MYCOBACTERIAL DISEASES

Peripheral blood cells from 29 patients with active Mycobacterium aviu m (MAC) or Mycobacterium tuberculosis diseases were tested for mycobac terial antigen-induced interferon (IFN)-gamma and interleukin (IL)-4 p roduction. Among MAC patients, human immunodeficiency virus (HIV) infe ction was associated with an 80% decrease in those who produced IFN-ga mma, resulting in a predominantly type 2 cytokine profile. HIV infecti on in patients with tuberculosis correlates with a 37% increase in tho se producing IL-4 and a type 1 to type 0 profile shift. These qualitat ive changes were independent of CD4(+) or CD8(+) cell numbers. The amo unts of both IFN-gamma and IL-4 were decreased in the HIV-infected pop ulation. Quantitative reduction of IFN-gamma was the result of fewer s ecreting cells rather than a down-regulation at the single-cell level. Disseminated disease was restricted to 2 of 5 HIV-infected MAC patien ts with a type 2 cytokine profile and 4 of 5 HIV-infected tuberculosis patients with a type 0 profile, These results demonstrated a shift in mycobacterial antigen-specific cytokine profiles from type I to type 0 and to type 2, in parallel with AIDS progression.