Thymic volume is associated independently with the magnitude of short- and long-term repopulation of CD4+ T cells in HIV-infected adults after highly active antiretroviral therapy (HAART)

Abstract

SUMMARYAge is one of the main factors involved in the rapidity and the magnitude of CD4 + T cell repopulation in human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART). Improved thymic function has been suggested as the main factor associated with CD4 + T cell restoration after HAART. This work was undertaken to determine, among host factors, the predictor variable at baseline involved in the magnitude of short-and long-term recovery of CD4 + T cells after HAART. HIV-RNA levels and CD4 + T cell numbers were determined in 54 HIV-infected adults at baseline and at weeks 4, 12, 48 and 96 after HAART. T cell subpopulations were determined by flow cytometry, thymic volume by computed tomography, T cell receptor excision circle (TREC)-bearing cells by quantitative polymerase chian reaction (PCR) and interleukin (IL)-7 levels by enzyme linked immunosorbent assay at baseline. The phenotype of patients' isolates was determined by infecting GHOST cells expressing CCR5 and CXCR4. The possible interference of phenotype with thymic function was also analysed. Baseline thymic volume was associated independently with the magnitude of short-and long-term recovery of CD4 + T cells after HAART, despite the patients' viral phenotype. The measurement of thymic volume before therapy may predict the magnitude of T cell increase. This result could have important clinical implications not only in HIV-infected patients, but also in other scenarios of T cell depletion such as bone marrow transplantation and chemotherapy.

Thymic Function in Severely Immunodeficient HIV Type 1-Infected Patients Receiving Stable and Effective Antiretroviral Therapy

“…1 Following the initial redistribution and expansion of peripheral memory T cells that occur during the first year of ART, 2,3 the recovery of CD4 ϩ T cells is attributed to the production of naive T cells, which is positively associated with thymus size before and after ART in both children 4,5 and adults. [6][7][8][9][10][11] Poor recovery of CD4 ϩ T cells in HIV patients who have received ART for several years may therefore reflect impaired thymic function. 12 However, some very immunodeficient patients experience substantial increases in CD4 ϩ T cell counts on ART ("CD4 ϩ T cell exploders"), associated with increased naive CD4 ϩ T cells and T cell receptor excision circle (TREC) content in CD4 ϩ T cells [a marker of recent thymic emigrants (RTE)], despite having minimal thymic tissue.…”

Sticking Up for the Immune System Integrity: Should the Thymus Be Preserved During Cardiac Surgery?

“…Due to its anatomical situation (in the anterior mediastinum, above the heart and ahead the great vessels) thymic biopsies are formally contraindicated and indirect measurements are needed. Thymic volume determination by thoracic computed tomography (CT) or magnetic resonance imaging (MRI) is an accurate indirect approximation and has been very useful to determine the role of thymic function in HIV-infected patients' immune reconstitution (Ruiz-Mateos et al 2004). Nevertheless, both are expensive techniques where thymic inference needs specifically trained radiologists.…”

TROCAI (Tropism Coreceptor Assay Information): a New Phenotypic Tropism Test and Its Correlation with Trofile Enhanced Sensitivity and Genotypic Approaches

“…TROCAI is based on the production of viral isolates from patients through improvement of a coculture technique previously published by our group (22) and multiple rounds of infection of indicator cells. TROCAI consists of two main steps as follows.…”

“…In this study, we developed a new phenotypic HIV-1 tropism assay (TROCAI [tropism coreceptor assay information]) based on the production of viral isolates from patients and multiple rounds of infection of indicator cells, modifying a technique previously reported by our group (22). In parallel, we have shown and recently extended the findings that the virological response to a short-term exposure to MRV could be used to predict the indication for CCR5 receptor antagonists, the maraviroc clinical test (MCT) (10,11).…”