SELECTIVE LOSS OF T-CELL FUNCTIONS IN DIFFERENT STAGES OF HIV-INFECTION - EARLY LOSS OF ANTI-CD3-INDUCED T-CELL PROLIFERATION FOLLOWED BY DECREASED ANTI-CD3-INDUCED CYTOTOXIC LYMPHOCYTE-T GENERATION IN AIDS-RELATED COMPLEX AND AIDS

To investigate the effects of persistant human immunodeficiency virus (HIV) infectionon T cell reactivity, functional properties of peripheral blood T cells from HIV‐seropositive homosexual men in various stages of infection were studied. T cell activationvia CD3 resulting in proliferation and differentiation was measured in a model system independent of accessory cells, using immobilized anti‐CD3 monoclonal antibodies (mAb). T cells from HIV‐infected asymptomatic men had a decreased proliferative response compared to HIV‐negative controls. T cells from AIDS‐related complex (ARC) and AIDS patients, compared to T cells from asymptomatic HIV‐infected men, had a significantly lower proliferative response to anti‐CD3 mAb. This diminished response to anti‐CD3 mAb was shown to be due to decreased interleukin (IL)2 productionand could be enhanced by co‐stimulation with anti‐CD28 mAb or by adding IL2. Anti‐CD3‐induced generation of cytotoxic T lymphocytes was fully intact in early infection but was severely decreased in T cells from ARC and AIDS patients. Cytotoxic activity could be restored to near normal levels after co‐stimulation with either anti‐CD28 mAb or IL2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL2 production after stimulation via the CD3/T cell receptor complex. In early HIV infection this seems to be predominantly caused by a specific loss of memory T cells. However, in later stages of infection when both naive and memory T cell subsets are depleted, resultingin a normal naive/memory T cell ratio, T cell functions further deteriorate probably due to intrinsic activation defects. These findings may be of pathogenic relevance since diminished T cell reactivity may facilitate spreading and replication of virulent HIV variants heralding development of ARC and AIDS. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim