HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis |
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| Authors: | G Marchetti A Riva M Cesari G M Bellistrì E Gianelli A Casabianca C Orlandi M Magnani L Meroni A d'Arminio Monforte C Mussini A Cossarizza M Galli A Gori for the Elvis Study Group |
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| Institution: | Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, San Paolo Hospital,;Department of Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy,;Institute of Biological Chemistry Giorgio Fornaini, University of Urbino, Urbino, Italy,;Infectious Diseases Clinics Azienda Ospedaliero, Universitaria Policlinico di Modena, Modena, Italy,;Department of Biomedical Sciences, University of Modena, Modena, Italy and;Division of Infectious Diseases, San Gerardo Hospital, Monza, Italy |
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| Abstract: | Background We hypothesized that there may be a correlation between the interleukin‐7 (IL‐7)/IL‐7 receptor (IL‐7R) regulatory system and parameters of T‐cell homeostasis in HIV‐infected long‐term nonprogressors (LTNPs) as compared with patients with disease progression. Methods The possibility of a correlation between T‐cell homeostatic parameters and IL‐7/IL‐7R was investigated in 22 LTNPs (CD4 count ≥500 cells/μL for >10 years) vs. HIV‐positive patients at different disease stages 12 early: CD4 count ≥400 cells/μL; 15 late (AIDS‐presenters): CD4 count ≤150 cells/μL]. Results Compared with early‐stage HIV‐positive patients, LTNPs displayed a higher circulating IL‐7 concentration (P=0.05), which was positively associated with higher IL‐7Rα expression and a higher T‐cell receptor excision circle (TREC) content specifically within CD4 cells (P<0.05). Compared with late‐stage disease patients, early‐stage disease patients displayed a lower IL‐7 concentration (P<0.01) and higher percentages of IL‐7Rα+ CD4 and CD8 cells (P=0.05). IL‐7 was positively correlated with the percentage of TREC+ CD4 cells (P<0.01), which translated into a higher percentage of naïve CD4 cells in early‐stage disease patients than in late‐stage disease patients; however, the CD4 cells in early‐stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (P<0.05). In late‐stage AIDS‐developing patients, substantially increased IL‐7 was correlated with a decreased percentage of IL‐7Rα+ CD4 cells (P=0.01), which resulted in these patients having a significantly lower percentage of naïve T cells (P<0.01) and a significantly lower content of TREC (P<0.01) than the other patients. Conclusions The maintenance of high CD4 cell counts in LTNPs was associated with a specific IL‐7/IL‐7R pattern characterized by increased IL‐7 and highest IL‐7Rα‐expressing CD4 cells relative to other patients. Compared with patients with late‐stage disease, LTNPs displayed a phenotypically naïve, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL‐7‐mediated pathway specifically sustaining peripheral CD4 counts. |
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| Keywords: | interleukin-7/interleukin-7R LTNP T-cell homeostasis |
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