TCR expression and clonality analysis in peripheral blood and lymph nodes of HIV-infected patients

Hum Immunol. 1997 Oct;57(2):93-103. doi: 10.1016/s0198-8859(97)00205-x.

Abstract

We compared the T cell receptor (TCR) V beta gene family repertoire in peripheral blood mononuclear cells (PBMC) and lymph node (LN) cells from 7 human immunodeficiency virus (HIV)-infected patients and 3 seronegative healthy controls. Virtually all the V beta family specificities were represented in patient PBMC and LN cells, and mean values for each specificity were comparable to figures in seronegative controls. In 4 patients, however, some V beta gene segment transcripts were overrepresented in the LN compartment, compared to the peripheral blood counterpart. To ascertain whether this phenomenon was due to polyclonal or oligoclonal expansion of T cells bearing the relevant V beta gene product, we sequenced the entire CDR3 region of a panel of 238 PCR clones corresponding to the V beta transcripts expanded in LN; as control, the same regions were cloned and sequenced in patient's PBMC, and in PBMC and LN cells from seronegative individuals. This analysis disclosed preferential usage of J beta 2 genes in PBMC and LN cells from both seropositive patients and controls, regardless of the V beta gene segment considered, thus indicating that this skewness in the V beta-J beta repertoire could be a consistent feature of at least a part of the V beta repertoire in different lymphoid compartments, regardless of the pathologic conditions. In addition, in LN from HIV seropositive patients we found the presence of recurrent TCR rearrangements, accounting for 8-23% of the generated clones, in each of the 4 V beta specificities analyzed; recurrent sequences were not found in PBMC from patients nor in PBMC and LN cells from seronegative controls. These findings suggest that antigen-driven oligoclonal T cell expansions may occur in vivo in lymphoid organs of HIV seropositive patients.

Publication types

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

MeSH terms

  • CD4 Lymphocyte Count
  • Clone Cells
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Gene Expression
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor beta*
  • HIV Infections / blood*
  • HIV Infections / immunology*
  • HIV Seronegativity
  • Humans
  • Lymph Nodes / immunology*
  • Polymerase Chain Reaction
  • RNA / genetics
  • RNA, Viral / analysis
  • Sequence Analysis, RNA
  • T-Lymphocytes / immunology*
  • Transcription, Genetic

Substances

  • DNA, Complementary
  • RNA, Viral
  • RNA