Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis |
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Authors: | Steffanie Sabbaj Michael F Para Robert J Fass Patrick W Adams Charles G Orosz Caroline C Whitacre |
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Institution: | (1) AIDS Clinical Trials Unit, Department of Medical Microbiology and Immunology, The Ohio State University, 43210 Columbus, Ohio;(2) Department of Internal Medicine, The Ohio State University, 43210 Columbus, Ohio;(3) Department of Surgery, The Ohio State University, 43210 Columbus, Ohio;(4) Department of Medical Microbiology and Immunology, The Ohio State University, 6072 Graves Hall, 333 West Tenth Avenue, 43210 Columbus, Ohio |
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Abstract: | The lymphocyte proliferative response to recall antigens is lost following HIV infection. We sought to devise a means by which the functional immune status of persons in the early stages of HIV infection could be monitored quantitatively. The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. Our data show that the limiting dilution analysis detects tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44% by proliferation. However, the frequency of tetanus-reactive T cells in HIV-infected individuals (median frequency = 1/59,156) is decrease five-fold as compared to seronegative controls (median frequency = 1/11,599). Longitudinal studies demonstrated a time-dependent decrease in the frequency of tetanus-specific T cell responses in the HIV-infected individuals. Thus, the limiting dilution analysis is a quantitative approach for detecting antigen-specific T cells in HIV-infected individuals, and may be used to monitor changes in T cell function in HIV infection. |
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Keywords: | T lymphocyte proliferation limiting dilution analysis tetanus immune response interleukin 2 acquired immunodeficiency syndrome immune function human immunodeficiency virus (HIV) infection |
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