Expression of Interleukin-7 Receptor and Activation Markers on Central Memory CD8 Cells in HIV-Infected Individuals Treated with Antiretrovirals.

We have recently shown that high levels of interleukin-7 (IL-7) predict poor virological response in HIV-1-infected patients. To understand the underlying mechanisms associated with increase in IL-7 levels, we assess the expression of IL-7 receptor and activation markers on different CD8 subsets in there well defined groups of patients including successfully treated (ST; n=8), untreated (UT; n=6), failing HAART due to drug resistance (FT; n=12) and healthy subjects (n=5).

The expression of IL-7/IL-2 receptors (CD127/CD25) and activation markers (CD38/HLA-DR) on CD8 naïve cells (CD45RA⁺CCR7⁺CD27⁺), central memory (T_CM; CD45RA⁻CCR7⁺CD27⁺), pre-terminal effector memory (T_PEM; CD45RA⁻CCR7⁻CD27⁻) and terminal effector memory cells (T_TEM; CD45RA⁺CCR7⁻CD27⁻) was measured in fresh blood samples using 8-color flow cytometry. Mann Whitney U test and Spearman correlation were used.

Although there was a trend toward a decrease in naïve, T_CM, T_PEM and T_TEM cells from ST to UT and then to FT, this did not reach significance (P=0.09). FT and UT subjects showed higher number of CD8 activated cells than ST or controls (22%, 20%, 3% and 4% respectively; P=0.07). Similarly, the percentages of T_CM activated cells were significantly higher in FT and UT than ST or controls (28%, 27%, 7% and 0.07%; P=0.02), whereas naïve and T_TEM activated cells were similar in all groups. Interestingly, the percentage of T_CM cells expressing CD127⁺CD25⁺ was lower in FT compared to UT or ST (0.7%, 2.1 and 7.4%; P=0.02). A strong positive correlation was observed between viral load and CD8⁺ or T_CM activated cells (r=0.46, P=0.02; r=0.65, P=0.004 respectively) but not with naïve CD8⁺ cells. These data suggest that a substantial proportion of T_CM but not naïve, T_PEM and T_TEM cells expressing immune activation markers with lower IL-7 receptor expression is present in subjects with persistent antigen stimulation, thus providing an explanation for increasing circulating IL-7 levels.