Eur J Immunol. 1994 Dec;24(12):3044-9. Unique Identifier : AIDSLINE
While V gamma 9/V delta 2 cells dominate among peripheral blood gamma
delta T cells in healthy adults, the majority of gamma delta T cells in
most HIV-1-infected individuals express V delta 1. We asked whether
these elevated levels of V delta 1 T cells were due to clonal expansion.
Three-color flow cytometry with monoclonal antibodies against V gamma
2/V gamma 3/V gamma 4, V gamma 4 and V gamma 9 was used to investigate V
gamma usage in 27 patients with elevated numbers of V delta 1 T cells.
While the relative proportion of V gamma 9 cells among gamma delta T
cells was significantly reduced in HIV-1+ individuals (10 +/- 11% vs. 80
+/- 17%, p < 0.001), the fraction of gamma delta T cells using V gamma 5
or V gamma 8 was significantly increased (54 +/- 15% vs. 7 +/- 11%, p <
0.001). In 1 patient, 76% of the V delta 1 cells expressed V gamma 2 or
V gamma 3, suggesting clonality of the V delta 1 population. In line
with this assumption, analysis of the V delta 1-J delta junctional
regions by reverse transcription-polymerase chain reaction (RT-PCR)
resulted in products of only one junctional length, as demonstrated by
electrophoresis on denaturing gels, and 12 out of 16 (75%) in-frame
junctional sequences were identical in this patient. In other HIV-1+
patients, RT-PCR resulted in products of several distinct sizes, also
indicating a highly restricted repertoire. After sequencing the V delta
1-J delta junctional regions of 3 additional patients, we found repeated
but patient-specific in-frame junctions accounting for 10-30% of the
sequenced clones. However, limited V delta 1-J delta junctional
diversity was also seen in healthy donors. RT-PCR products from 10
healthy individuals resulted in distinct bands on denaturing gels. In 1
of them exhibiting a single prominent band, 10 out of 17 (58%) sequenced
junctions were identical. Two other healthy donors displayed 2/14 and
5/18 identical junctional sequences, respectively. Taken together, our
results reveal significant alterations of V gamma usage in HIV-1+
patients, while the V delta 1 junctional repertoire is similarly
restricted in HIV-1+ and HIV-1- individuals. Therefore, these data argue
against an obligatory clonal expansion of V delta 1-expressing cells
during HIV-1 infection.
Base Sequence CD4 Lymphocyte Count DNA Primers/CHEMISTRY Flow
Cytometry Gene Expression Gene Rearrangement, delta-Chain T-Cell
Antigen Receptor Gene Rearrangement, gamma-Chain T-Cell Antigen
Receptor Genes, Structural Human HIV Infections/*IMMUNOLOGY
Molecular Sequence Data Receptors, Antigen, T-Cell,
gamma-delta/CLASSIFICATION/*GENETICS RNA, Messenger/GENETICS Support,
Non-U.S. Gov't T-Lymphocyte Subsets/*IMMUNOLOGY JOURNAL ARTICLE