Diminished Interferon Gamma Production May Be the Earliest Indicator of Infection with the Human Immunodeficiency Virus

The degree of clinical severity in human immunodeficiency virus infected patients, ranging from asymptomatic seropositive subjects to acquired immure deficiency syndrome, as well as in individuals at risk was assessed in relation to: (1) T-cell subset balance and expression of markers of T-cell activation; (2) natural killer activity; and (3) interferon gamma production. A decrease in the CD4/CD8 (helper/suppressor) ratio and an increase in the percentage of CD8+ (suppressor/cytotoxic) cells coexpressing markers of activation (HLA-DR or CD25) were closely correlated with the clinical severity of the human immunodeficiency virus infection. Natural killer activity was significantly impaired in patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex but normal in asymptomatic seropositive individuals and subjects at risk. Interferon gamma production, either in response to mitogens or the antigens from infectious agents commonly affecting human immunodeficiency virus-positive individuals, was decreased in patients with acquired immune deficiency syndrome or acquired immune deficiency syndrome-related complex, with lesser involvement in human immunodeficiency virus-seropositive subjects or individuals at risk. Four of the six persons in the last group seroconverted during the ten months subsequent to evaluation of their immune status. Since production of interferon gamma was diminished in these patients while other assays of immunity were normal, measurement of this lymphokine may be a useful determinant of infection with the human immunodeficiency virus.