Activated peripheral CD8 lymphocytes express CD4 in vivo and are targets for infection by human immunodeficiency virus type 1

S Imlach, S McBreen, T Shirafuji, C Leen, J E Bell, P Simmonds

Research output: Contribution to journalArticlepeer-review

Abstract

There is increasing evidence that CD8 lymphocytes may represent targets for infection by human immunodeficiency virus type 1 (HIV-1) in vivo whose destruction may contribute to the loss of immune function underlying AIDS. HIV-1 may infect thymic precursor cells destined to become CD4 and CD8 lymphocytes and contribute to the numerical decline in both subsets on disease progression. There is also evidence for the induction of CD4 expression and susceptibility to infection by HIV-1 of CD8 lymphocytes activated in vitro. To investigate the relationship between CD8 activation and infection by HIV-1 in vivo, activated subsets of CD8 lymphocytes in peripheral blood mononuclear cells (PBMCs) of HIV-seropositive individuals were investigated for CD4 expression and HIV infection. Activated CD8 lymphocytes were identified by expression of CD69, CD71, and the human leukocyte antigen (HLA) class II, the beta-chain of CD8, and the RO isoform of CD45. CD4(+) and CD4(-) CD8 lymphocytes, CD4 lymphocytes, other T cells, and non-T cells were purified using paramagnetic beads, and proviral sequences were quantified by PCR using primers from the long terminal repeat region. Frequencies of activated CD8 lymphocytes were higher in HIV-infected study subjects than in seronegative controls, and they frequently coexpressed CD4 (mean frequencies on CD69(+), CD71(+), and HLA class II(+) cells of 23, 37, and 8%, respectively, compared with 1 to 2% for nonactivated CD8 lymphocytes). The level of CD4 expression of the double-positive population approached that of mature CD4 lymphocytes. That CD4 expression renders CD8 cell susceptible to infection was indicated by their high frequency of infection in vivo; infected CD4(+) CD8 lymphocytes accounted for between 3 and 72% of the total proviral load in PBMCs from five of the eight study subjects investigated, despite these cells representing a small component of the PBMC population (
Original languageEnglish
Pages (from-to)11555-64
Number of pages10
JournalJournal of Virology
Volume75
Issue number23
DOIs
Publication statusPublished - Dec 2001

Keywords

  • Adult
  • Antigens, CD4
  • Antigens, CD45
  • Base Sequence
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Case-Control Studies
  • DNA Primers
  • Female
  • HIV-1
  • Humans
  • Immunomagnetic Separation
  • Immunophenotyping
  • Male
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Proviruses
  • T-Lymphocyte Subsets
  • Viral Load

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