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CD4+CD45R0+CD127-CCR5+ T Cells Define the Expansion of CD127- T Cells in HIV+ Individuals
Samandhy Cedeno*, A Llano, B Clotet, and J Este
Fndn irsiCaixa, Badalona, Spain
Background: Interleukin-7 (IL-7) is known to be a key
cytokine in T cell development and proliferation. In HIV infection, increased
IL-7 levels in plasma correlate to high plasma viral load and decreased CD4+
cell numbers. Similarly, T cells expressing the IL-7 receptor CD127 are reduced
in HIV+ individuals suggesting a preferential loss of CD127+
cells. Here, we provide evidence for the preferential loss of CD127+,
CCR5+, memory, CD4+ T cells in HIV infection and the
increased proliferation of the CD127−, CCR5+
subtype.
Methods: We have studied the expression of CD127 in
different lymphocyte subpopulations in HIV-infected individuals and HIV
negative donors. We used 4-color flow cytometry analysis of CD3, CD4, CD127,
CD45RO, CCR5, and CXCR4; IL-7 levels were measured by ELISA in plasma. Plasma
viral load and absolute CD4 and CD8 cell counts were measured by the amplicor
test or flow cytometry, respectively. Non-parametric t-test (Mann-Whitney) and Spearman´s coefficient were used to
establish significant differences and correlations among different parameters.
Results: Mean viral
load and
CD4 cell counts were 5.14±5.6 log copies/mL and 475±278 cell/µL. Mean IL-7 was
4.4±3 pg/mL in a cohort of 54 HIV+ individuals. The proportion of
CD127 negative T cells were significantly (p
= 0.0009) higher in HIV+ individuals than in HIV−
donors. The proportion of CD127– T cells correlates (r = 0.69, p = 0.004) with viral load and inversely with CD4
T cell numbers (r = –0.67, p = 0.007). Therefore, HIV+
individuals with low CD4 T cells showed an increased proportion of CD127–
cells. Furthermore, HIV+ individuals showed an increased proportion
of memory (CD45RO+) CD4+CD127– cells as
compared to negative donors. In this cell subset the proportion of CCR5+
cells, but not CCR5– or CXCR4+ was increased (p = 0.0009) when comparing to HIV–
donors.
Conclusions: The CD4+CD45R0+CD127–CCR5+
T subpopulation could better define the observed increase in the percentage of
CD127– T cells in HIV+ individuals suggesting that the
preferential expansion of this subpopulation or a specific depletion of CD4+CD45R0+CD127+CCR5+
T cells as a consequence of infection.
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