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. © 2009 British HIV Association.
HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis
CONCIA, Ercole;
2009-01-01
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. © 2009 British HIV Association.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.