Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy

J Infect Dis. 2001 Mar 1;183(5):722-9. doi: 10.1086/318816. Epub 2001 Feb 1.

Abstract

Cytotoxic T lymphocytes (CTLs) are an important defense against human immunodeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppressing replication, the evolution of T cell phenotypes and HIV-specific CD8+ lymphocytes was prospectively investigated in 41 patients initiating combination therapy. Suppression of viremia to <200 copies/mL was associated with increases in naive cells (CD45RA+62L+) and declines in activated T cells (CD95+ cell counts and CD38+ HLA-DR+). HIV-specific tetramer-staining CD8+ T cells were detected in 6 of 10 HLA-A*0201-positive persons, which declined in 5 with treatment. CTL precursor frequencies were markedly consistent before and after treatment. Eight (72%) of 11 recognized > or =1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8+ T cells, including those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capable of differentiating into effectors remains stable, and the recognition of new epitopes may occur.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Dose-Response Relationship, Immunologic
  • Drug Therapy, Combination
  • Epitopes, T-Lymphocyte / immunology
  • Flow Cytometry
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • HLA-DR Antigens / analysis
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunohistochemistry
  • Immunophenotyping
  • Indinavir / pharmacology
  • Indinavir / therapeutic use
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use
  • Leukocyte Common Antigens / analysis*
  • Prospective Studies
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Load
  • Zidovudine / pharmacology
  • Zidovudine / therapeutic use

Substances

  • Anti-HIV Agents
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • Immunodominant Epitopes
  • Lamivudine
  • Zidovudine
  • Indinavir
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1