title: 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.
abstract: 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.
authors.affiliation: Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: R A
authors.initials: RA
authors.lastname: Gruters
authors.forename: F G
authors.initials: FG
authors.lastname: Terpstra
authors.forename: R
authors.initials: R
authors.lastname: De Jong
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Noesel
authors.forename: R A
authors.initials: RA
authors.lastname: Van Lier
authors.forename: F
authors.initials: F
authors.lastname: Miedema
mesh_terms: D000386:AIDS-Related Complex / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000502:physiology; D018106:CD28 Antigens; D017252:CD3 Complex; D002454:Cell Differentiation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell