Effects of different antigenic stimuli on thymic function and interleukin-7/CD127 system in patients with chronic HIV infection.

BACKGROUND

We tested if an increase in immune activation and a decrease in CD4⁺ T cells induced by different antigenic stimuli could be associated with changes in the thymic function and the interleukin (IL)-7/CD127 system.

METHODS

Twenty-six HIV-infected patients under combined antiretroviral therapy (cART) were randomized to receive, during 12 months, a complete immunization schedule (7 vaccines and 15 doses) or placebo. Thereafter, cART was interrupted during 6 months. Changes in the thymic function and the IL-7/CD127 system after 3 different antigenic stimuli (vaccines, episodes of low-level intermittent viremia before cART interruption, or viral load rebound after cART interruption) were assessed.

RESULTS

During the period on cART, neither vaccines nor low-level viremia influenced thymic function or IL-7/CD127 system parameters. By analyzing the cohort as a whole while on cART, a significant improvement was observed in the thymic function as measured by an increase in the thymic volume (P = 0.024), T-cell receptor excision circle-bearing cells (P = 0.012), and naive CD4⁺ and CD8⁺ T cells (P = 0.069 both). No significant changes were observed in the IL-7/CD127 system. After cART interruption, a decrease in T-cell receptor excision circles (P < 0.001) and naive CD8⁺ T cells (P < 0.001), an increase in IL-7 and expression of CD127 on naive and memory CD4⁺ T cells (P = 0.028, P = 0.088, and P = 0.04, respectively), and a significant decrease in CD127 on naive and memory CD8⁺ T cells (P = 0.01, P = 0.006, respectively) were observed.

CONCLUSIONS

Low-level transient antigenic stimuli during cART were not associated with changes in the thymic function or the IL-7/CD127 system. Conversely, viral load rebound very early after cART interruption influenced the thymic function and the IL-7/CD127 system. Clinical Trials.gov number NCT00329251.