Decreased ability of HIV-1 tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells.
It has been shown in several animal models that HIV infection of accessory cells (ACs) plays an important role in development of AIDS. Here, we report that ACs treated with HIV-1 Tat protein (Tat-ACs) have a decreased ability to organize cellular aggregates as compared with untreated ACs, resulting in incomplete activation of T cells in responses to anti-CD3 mAb or staphylococcal enterotoxin B stimulation. The T cells failed to up-regulate adhesion molecules CD11a and CD2 on the cell surface and had reduced proliferative responses, as determined by [3H]thymidine incorporation, but they obtained lymphoblast-like morphology and expressed early activation antigens on the cell surface such as Fas and CD69 and interleukin 2 receptor, at comparable levels as those T cells undergoing a maximal proliferation. These results suggest that the Tat-AC-induced defect occurs in the late, but not in the early, phases of T cell activation. Normal expression of cell surface Fas antigen accompanied by defects in late activation thus may result in the susceptibility of these T cells to apoptosis. Our studies suggest that dysfunction, hyperactivation, and susceptibility to apoptosis, as observed with T cells isolated from HIV-infected individuals, may be, at least in part, a consequence of abnormal functions of ACs.
Wu
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MX
Division of Tumor Immunology, Room 751, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. mei@mbcrr.harvard.edu
Schlossman
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SF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D017209:Apoptosis; D002449:Cell Aggregation; D002455:Cell Division; D015696:Gene Products, tat / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus