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Frequency and function of HIV-specific CD8(+) T cells.

S A Migueles1, M Connors

  • 1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11B-09, 10 Center Dr MSC 1876, Bethesda, MD 20892-1876, USA.

Immunology Letters
|October 12, 2001
PubMed
Summary

High numbers of HIV-specific CD8(+) T cells are present even in patients with high viral loads. Qualitative aspects of these T cell responses, not just frequency, may distinguish long-term nonprogressors from those with progressive HIV infection.

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Area of Science:

  • Immunology
  • Virology
  • Infectious Diseases

Background:

  • CD8(+) T cells play a crucial role in controlling viral infections, including Human Immunodeficiency Virus (HIV).
  • Long-term nonprogressors (LTNP) represent a unique cohort of HIV-infected individuals who maintain normal CD4(+) T cell counts and low viral loads without antiretroviral therapy.
  • Understanding the characteristics of virus-specific CD8(+) T cell responses is vital for developing effective HIV therapies and vaccines.

Purpose of the Study:

  • To investigate the frequencies and characteristics of HIV-specific CD8(+) T cell responses in a cohort of HIV-infected patients, including LTNP.
  • To determine the correlation between the magnitude of HIV-specific CD8(+) T cell responses and plasma viral load.
  • To explore whether the breadth and qualitative aspects of CD8(+) T cell responses differ between nonprogressors and patients with progressive HIV infection.

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Main Methods:

  • Studied 27 HIV-infected patients, including LTNP, analyzing virus-specific CD8(+) T cell responses.
  • Measured CD8(+) T cell frequencies responding to HIV antigens using flow cytometry and intracellular interferon-gamma (IFN-gamma) detection.
  • Utilized autologous B cells infected with HIV-vaccinia recombinant for antigen stimulation.

Main Results:

  • High frequencies (1.4-22%) of circulating HIV-specific CD8(+) T cells were detected, irrespective of plasma viral load.
  • The majority of HIV-specific CD8(+) T cells responded to Gag-Pol gene products.
  • While frequencies of peptide-specific CD8(+) T cells were similar, the breadth of responses was greater in patients with progressive HIV infection compared to LTNP.

Conclusions:

  • High numbers of HIV-specific CD8(+) T cells are present even in individuals with high viremia and progressive disease.
  • The frequency of HIV-specific CD8(+) T cells alone does not correlate with plasma viremia levels.
  • Qualitative differences in CD8(+) T cell responses may be key in distinguishing LTNP from patients with progressive HIV infection.