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Effects of Different Antigenic Stimuli on Thymic Function and Interleukin-7/CD127 System in Patients with Chronic HIV Infection

Castro, Pedro MD, PhD*; Torres, Berta MD; López, Anna MD, PhD; González, Raquel MD§,‖; Vilella, Anna MD, PhD§,‖; Nicolas, Jose M. MD, PhD*; Gallart, Teresa MD‡,¶; Pumarola, Tomàs MD, PhD#; Sánchez, Marcelo MD, PhD**; Leal, Manuel MD, PhD††; Vallejo, Alejandro MD, PhD††; Bayas, José M. MD, PhD§; Gatell, José M. MD, PhD; Plana, Montserrat MD, PhD; García, Felipe MD, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2014 - Volume 66 - Issue 5 - p 466–472
doi: 10.1097/QAI.0000000000000207
Basic and Translational Science

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.

*Medical Intensive Care Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

Infectious Diseases Unit, HIVACAT HIV Vaccine Development in Catalonia, Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

Retrovirology and Viral Immunopathology Laboratories, HIVACAT, Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

§Preventive Medicine Department Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Spain;

Immunology Laboratory, Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

#Microbiology Laboratory, Hospital Clínic, IDIBAPS, University of Barcelona, Spain;

**Radiology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Spain; and

††Infectious Diseases Service, IBIS, Hospital Universitario Virgen del Rocio, Seville, Spain (Anna López is now with the Molecular and Translational Oncology Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, Spain).

Correspondence to: Felipe García, MD, PhD, Infectious Diseases Unit, Hospital Clínic, Villarroel, 170, 08036 Barcelona, Spain (e-mail: fgarcia@clinic.ub.es).

Partially supported by Grants: SAF 2012-39075, FIS PI10/02984, PS09/01297 FIS PI070291, FIS PI1200969, RIS [Red Temática Cooperativa de Grupos de Investigación en Sida del Fondo de Investigación Sanitaria (FIS)]. Dr. M.P. is a researcher from the IDIBAPS and is supported by the ISCIII (Instituto de Salud Carlos III) and the Health Department of the Catalan Government (Generalitat de Catalunya).

The authors have no conflicts of interest to disclose.

M.P. and F.G. have contributed equally.

Received December 17, 2013

Accepted April 02, 2014

© 2014 by Lippincott Williams & Wilkins