Comparative Proliferation Capacity of Gag-C-Specific Naive and Memory CD4+ and CD8+ T Lymphocytes in Rapid, Viremic Slow, and Slow Progressors During Human Immunodeficiency Virus Infection

Viral Immunol. 2018 Sep;31(7):513-524. doi: 10.1089/vim.2018.0012. Epub 2018 Aug 29.

Abstract

The exact cause of altered dynamics in T cells compartment during HIV infection remains elusive to date. In this longitudinal study, the proliferation frequency of different T cell subsets was investigated in untreated HIV-1-infected Indian individuals stratified as rapid (R), viremic slow (VS), slow (S) progressors, and healthy controls. Ten healthy and 20 treatment-naive HIV-1-infected individuals were enrolled. Expression of Ki67 nuclear antigen was examined on HIV-specific T cell subsets in peripheral blood lymphocytes. Upon stimulation with HIV-1 Gag-C peptide pools, effector memory (EM) CD4 T cells (R vs. S, EM CD4, p < 0.05) of R progressors proliferated significantly compared with those of S progressors at baseline. However, central memory (CM) CD8 T cell subsets proliferated significantly in VS and S progressors compared with those in R progressors, wherein highest proliferation frequency of EM CD8 T cells was observed. At follow-up visit, the proliferation frequency of naive CD8 T cells was significantly higher in R progressors than S progressors (R vs. S naive CD8, p < 0.05). The findings suggest altered dynamics of different CD4+ and CD8+ T cell subsets in R, VS, and S progressors. The increase in CM T cell proliferation in VS and S progressors could be attributed to slower progression of the HIV infection. Hence, treatment strategies must be focused on restoring the homeostatic balance to restore T cell functionality.

Keywords: HIV; Ki67 nuclear antigen; T cell exhaustion; flow cytometer; proliferation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation*
  • Cohort Studies
  • Disease Progression
  • Female
  • Gene Products, gag / immunology*
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunologic Memory*
  • Ki-67 Antigen / metabolism
  • Longitudinal Studies
  • Male
  • Viral Load
  • Viremia

Substances

  • Gene Products, gag
  • Ki-67 Antigen
  • MKI67 protein, human