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 T lymphocyte generation in AIDS-related complex and AIDS

Eur J Immunol. 1990 May;20(5):1039-44. doi: 10.1002/eji.1830200514.


To investigate the effects of persistant human immunodeficiency virus (HIV) infection on T cell reactivity, functional properties of peripheral blood T cells from HIV-seropositive homosexual men in various stages of infection were studied. T cell activation via 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 production and could be enhanced by co-stimulation with anti-CD28 mAb or by adding IL 2. 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 IL 2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL 2 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, resulting in 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Complex / immunology
  • Acquired Immunodeficiency Syndrome / immunology
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • CD28 Antigens
  • CD3 Complex
  • Cell Differentiation / immunology
  • HIV Infections / immunology*
  • Humans
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / physiology*
  • T-Lymphocytes, Cytotoxic / physiology
  • Time Factors


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD3 Complex
  • Interleukin-2
  • Receptors, Antigen, T-Cell