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

Abstract

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.

• Authors: Pedro Castro, Berta Torres, Anna López, Raquel González, Anna Vilella, Jose M Nicolas, Teresa Gallart, Tomàs Pumarola, Marcelo Sánchez, Manuel Leal, Alejandro Vallejo, José M Bayas, José M Gatell, Montserrat Plana, Felipe García
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 66 Issue 5 Pg. 466-72 (Aug 15 2014) ISSN: 1944-7884 [Electronic] United States
• PMID: 24820104 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• Anti-HIV Agents
• IL7 protein, human
• Interleukin-7
• Receptors, Interleukin-7

Topics

• AIDS Vaccines
• Adult
• Anti-HIV Agents
• CD4 Lymphocyte Count
• Chronic Disease
• Cohort Studies
• Double-Blind Method
• Female
• Gene Expression Regulation (immunology)
• HIV Infections (immunology, metabolism)
• Humans
• Interleukin-7 (genetics, metabolism)
• Male
• Middle Aged
• Receptors, Interleukin-7 (genetics, metabolism)
• Risk Factors
• Thymus Gland (physiology)
• Viral Load
• Viremia