Elsevier

Clinical Immunology

Volume 93, Issue 3, December 1999, Pages 245-249
Clinical Immunology

Regular Article
Lymphocyte Proliferation Assays May Underestimate Antigen Responsiveness in Human Immunodeficiency Virus Infection

https://doi.org/10.1006/clim.1999.4802Get rights and content

Abstract

The objective of this study was to examine the relationships among lymphocyte proliferation, interferon-γ (IFN-γ) production, and apoptosis in peripheral blood mononuclear cells (PBMC) of HIV-1-infected patients and controls. PBMC were prepared from 19 HIV-1-infected patients and 16 healthy controls. Using tetanus toxoid (TT) as a recall antigen, we assessed lymphocyte proliferation using [3H]thymidine incorporation after 2, 4, 6, and 7 days' culture and IFN-γ production in 48-h culture supernatants by ELISA. Apoptosis was measured using TdT-mediated dUTP nick-end labeling. Median stimulation indices (SIs) in HIV-1-infected patients were 2.8 and 3.7 as opposed to 24.9 and 25.1 in healthy controls after 6 and 7 days' culture, respectively (P < 0.001). Among the controls, peak proliferation was seen after 7 days in culture whereas in patients, SIs peaked at 4 days and fell progressively by days 6 and 7. At 2 and 4 days of stimulation with tetanus, patients' T cells showed increased apoptosis (19 and 25%) vs 12 and 15% apoptosis seen in controls' cells, P < 0.05. Interferon-γ in 48-h supernatants of TT-stimulated PBMC was comparable among patients and controls. Whereas in our system, 6 and 7 day assays of lymphocyte proliferation provide increasing responses to TT among healthy controls, these durations of culture may underestimate antigen responsiveness in HIV-1 infection. Cell death due to apoptosis may account for this phenomenon. Whether shorter term or longer term assays of lymphocyte responsiveness more accurately reflect in vivo immune competence is unknown. Nonetheless, shorter duration assays may provide a more realistic estimate of the frequency of antigen-reactive cells in persons with HIV-1 infection.

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  • Cited by (7)

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    Supported by NIH Grants AI-38858 and AI-36219.

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    To whom correspondence and reprint requests should be addressed at Division of Infectious Diseases, University Hospitals of Cleveland, AIDS Clinical Trials Unit, Foley Building 2106 Cornell Rd, Cleveland, OH 44106. E-mail: [email protected].

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