Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
V delta repertoire of gamma delta-T cells in peripheral lymphocytes during HIV-infection: cellular and molecular characterization of delta TCS1+ T cells.
Int Conf AIDS. 1993 Jun 6-11;9(1):199 (abstract no. PO-A19-0386). Unique Identifier : AIDSLINE MED/93333835 Madeleine C; Gilles D; Severine B; Muriel C; Luc M; Gougeon ML; Viral Oncology Unit, Pasteur Institute, Paris, France.
Abstract:
OBJECTIVES: Molecular and functionnal characterization of gamma delta T cells with V delta 1-J delta 1 gene rearrangements in PBL from normal versus HIV infected donors. Identification of the ligand(s) recognized by these T cells. METHODS: PBLs, T cell lines or clones were investigated for the expression of cell surface markers (CD3, alpha beta or gamma delta TCRs, CD25, CD38 and DR activation markers) by FACS analysis. Their gamma delta T cell rearrangements were studied by polymerase chain reaction PCR) using oligonucleotides specific of each of V, J and C gene segments. The TCRs rearrangements and the size distribution of CDR3, for a given cell population, were analysed at the same time on an Automatic DNA Sequencer as described by Cochet et al. (Eur. J. Immun., 1992, 22: 2639) and Pannetier et al. (P.N.A.S., 1993, in press). The phenotype of the T cell lines and clones was determined by FACS analysis. Their function was studied by standard assays. The structure of the gamma and delta chains were determined by conventional DNA sequencing. RESULTS: gamma delta T cells represent a minor fraction of CD3+ T cells, 3-10% of human PBLs. Among these the majority (70%) have a receptor constituted by V gamma 9-V delta 2 gene rearrangements. In HIV-infected patients we have previously shown that delta TCS1+ T cells, a subset of V delta 1+ T cells, increase with the progression of the disease as early as stage II. These cells are mainly CD8+ or double negative. We have analyzed in detail the repertoire of transcripts encoding the V delta chain from PBLs by PCR. We have found that, when compared to a group of healthy donors, all V delta 1-J delta s rearrangements present a distribution of sizes corresponding to a polyclonal population of cells, but only V delta 1-J delta 1 rearrangements show a distribution of sizes of the hypervariable CDR3 region increasing with the progression of the disease. Studies to determine the nature of the antigen(s) responsible for the enhancement of the V delta 1 sub-population are in progress on isolated gamma delta T cells. CONCLUSIONS: In the gamma delta T cell population of PBLs of HIV infected patients, we have shown a very strong correlation between the increase of CDR3 size of delta TCS1+ T cells and the progression of the disease. Characterization of T cell clones belonging to this group of cells is in progress and will be discussed.
Keywords: *Gene Rearrangement, delta-Chain T-Cell Antigen Receptor *HIV Infections/IMMUNOLOGY *Receptors, Antigen, T-Cell, gamma-delta/GENETICS *T-Lymphocyte Subsets 931130
M93B5283
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