T cell receptor excision circle (TREC) content following maximum HIV suppression is equivalent in HIV-infected and HIV-uninfected individuals

Background: The adult human thymus contributes to de novo T cell synthesis; such synthesis can be assessed by analyzing T cell receptor excision circl es (TREC). Methods: TREC levels were measured in total peripheral blood mononuclear ce lls (PBMC) and CD4- and CD8-enriched cells of 29 HIV-positive patients with maximal viral suppression. The expression of CD45RA+CD45RO-, CD45RA+CD62L, CD45RO-CD27+CD95low and HLA-DR+CD38+ was assessed using three-color flow cytometric analysis of whole blood, Thymic index score was based on compute d tomographic scans of the thymus. The relationship of TREC with thymic ind ex and the expression of the naive phenotypes was evaluated. Results: TREC expression was not statistically different in these HIV-posit ive patients from that in age-matched HIV-negative controls. Among HIV-posi tive patients with CD4 cell count of > 500 x 10(6) cells/I after antiretrov iral therapy (n = 15), PBMC TREC levels correlated with the expression of C D45RA+CD45RO- and CD45RA+CD62L+ naive phenotypes, and inversely correlated with the expression of HLA-DR+CD38+. The change between pre- and post-thera py CD4 cell counts for these 15 patients significantly correlated with both thymic index and expression of the CD45RA+CD45RO- phenotype. Conclusions: The finding that TREC expression was equivalent between HIV-po sitive patients after therapy and HIV-negative donors suggests that there i s no reduction in thymic output among HIV-positive individuals after therap y. Given that TREC is inversely correlated with HLA-DR/CD38 expression, its analysis in studies of thymopoiesis should be evaluated in the context of maximum viral suppression to reduce HIV-mediated immune activation and/or b y normalizing for cell turnover. (C) 2001 Lippincott Williams & Wilkins.