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Profile of CD127 Expression in Different CD4 and CD8 T-cell Subsets in Patients with Chronic HIV Infection, and Changes during ART
Jose Benito*, M Lopez, S Lozano, A Cascajero, J Gonzalez-Lahoz, and V Soriano
Hosp Carlos III, Madrid, Spain
Background: CD127 expression is decreased in T cells of HIV+
patients, and tends to normalize on HAART. Recent attention has been paid to
this receptor as a potential tool in the clinical setting. We evaluated the
expression of CD127 in several CD4 and CD8 T-cell subsets, as well as the level
of activation and evolution of these cells during successful HAART.
Methods: We analyzed 22 HIV+ patients who initiated HAART
and maintained <50 HIV RNA copies/mL for 24
months. CD127, CD45RA, CD27, and CD38 were simultaneously measured on CD4 and
CD8 T cells by flow cytometry. CD38 was evaluated
using a quantitative assay. Interleukin-7 (IL-7) was measured with a highly
sensitivity ELISA. All measurements were performed at months 0, 12, and 24 of
HAART. A paired Students t-test was
used for comparisons at different time points. A multivariate linear regression
analysis was performed to examine the influence of IL-7, CD4, and HIV RNA on
CD127 expression.
Results: At baseline CD127 expression was similar in CD4 and CD8 T
cells. The lowest CD127 expression was seen in RA+27 (4%±7
and 15%±7 for CD4 and CD8) and the highest in RA27+
cells (55%±13 and 61%±27 for CD4 and CD8). Baseline activation was higher in
CD127 than in CD127+ cells, being the greatest
difference seen in the RA27+ subset (8123±3320 vs 1408±911 and 10735±4766 vs
1023±1027 CD38 molecules/cell for CD4 and CD8). IL-7 and HIV RNA inversely
correlated with several CD127+ T-cell subsets. Activation of total
CD8+ cells and of different CD127 and CD127+
subsets (except for RA+27+ cells) was negatively
correlated with CD4 count and positively with HIV RNA.
After 24 months on HAART, CD127
expression significantly increased on total CD8 cells and in all distinct
subsets but RA+27+ cells. Activation significantly
decreased in all CD8+ subsets but RA+27+ and
RA27+127 cells. Activation of CD4 cells
significantly decreased in RA27127 and RA27+127
subsets. CD4 increase at month 24 inversely correlated with activation of CD4+RA27+127+
cells and with CD127 expression on CD8+ cells.
Conclusions: CD127 expression in HIV infection is differentially
regulated in distinct CD4 and CD8 T-cell subsets. The level of activation is
higher in cells lacking this marker. HAART increases CD127 expression and
decreases activation mainly in CD127 cells; 2 of the CD127+
cell subsets showed a good correlation with the extent of CD4 reconstitution on
HAART, suggesting that this marker could be useful in the management of HIV+
patients.
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