HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis.
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 > or =500 cells/microL for >10 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count > or =400 cells/microL ; 15 late (AIDS-presenters): CD4 count < or =150 cells/microL ].


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-7Ralpha 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-7Ralpha+ 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-7Ralpha+ 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-7Ralpha-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.
Marchetti
G
G
Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, San Paolo Hospital, University of Milan, via A. di Rudiní, Milan 8-20142, Italy. giulia.marchetti@unimi.it
Riva
A
A
Cesari
M
M
Bellistrì
G M
GM
Gianelli
E
E
Casabianca
A
A
Orlandi
C
C
Magnani
M
M
Meroni
L
L
d'Arminio Monforte
A
A
Mussini
C
C
Cossarizza
A
A
Galli
M
M
Gori
A
A
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D020276:HIV Long-Term Survivors; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000276:immunology; D019394:Ki-67 Antigen / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000097:blood* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D015851:Interleukin-7; D019394:Ki-67 Antigen; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain