Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients.
OBJECTIVE
Elevated levels of interleukin (IL)-7 are present in the blood of HIV-positive patients and it is known that IL-7 receptor (IL-7R)alpha expression decreases on T cells during HIV infection. The subset(s) of T cells with low IL-7Ralpha and the consequence of low IL-7Ralpha expression for T-cell survival are poorly characterized.


METHODS
The frequency of IL-7Ralpha-negative T cells in HIV-positive patients was studied in relation to CD4 T-cell counts, IL-7 concentration and survival in culture. We analysed IL-7Ralpha expression in different T-cell populations and in relation to Bcl-2 expression.


METHODS
Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Ralpha and Bcl-2 expression in different T-cell populations was studied by flow cytometry. The influence of IL-7Ralpha expression on T-cell survival was studied by culturing T cells in the presence of IL-7.


RESULTS
Down-regulation of IL-7Ralpha on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Ralpha expression was associated with low Bcl-2 expression and with the reduced survival capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with memory phenotype showed a decreased IL-7Ralpha expression in association with CD28 down-regulation.


CONCLUSIONS
The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Ralpha down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.
Rethi
Bence
B
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. Bence.Rethi@mtc.ki.se
Fluur
Caroline
C
Atlas
Ann
A
Krzyzowska
Malgorzata
M
Mowafi
Frida
F
Grützmeier
Sven
S
De Milito
Angelo
A
Bellocco
Rino
R
Falk
Kerstin I
KI
Rajnavölgyi
Eva
E
Chiodi
Francesca
F
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000494:pharmacology; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D018106:CD28 Antigens; D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain