T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART.
OBJECTIVE
To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART.


METHODS
Thirty-five HIV-positive subjects on HAART for at least 1 year, all with undetectable HIV-1 RNA, were studied. Patients were defined as InR according to a CD4 cell increase < 20% from CD4 cell baseline or CD4 cell count < 200/microl; subjects with a CD4 T-cell increase > 20% from baseline and a CD4 cell count > 200/microl were defined as immunological responders (IR). We performed a comprehensive study to characterize the immune response of InR.


METHODS
The immunological phenotype of peripheral blood mononuclear cells, thymic naive T cells, T-cell receptor Vbeta repertoire, serum concentration of interleukin (IL)-7, the expression of IL-7Ralpha on naive and memory CD4 and CD8 T cells, and regulatory T cells (Treg) were studied.


RESULTS
In InR a significant reduction (P < 0.0001) of naive and thymic naive CD4 T cells was associated with a reduced expression of IL-7Ralpha in both cell subsets, with an increased serum concentration of IL-7 was observed. Furthermore, an increased immune activation with a reduced Treg frequency and increased number of expansions of Vbeta families was observed.


CONCLUSIONS
The reduced expression of IL-7Ralpha associated with the persistent immune activation and the alteration of Treg frequencies in part explains the low level of CD4 T cells observed in InR.
Marziali
Marco
M
Department of Clinical Medicine, University of Rome "La Sapienza", Italy.
De Santis
Wladimiro
W
Carello
Rossella
R
Leti
Wilma
W
Esposito
Antonella
A
Isgrò
Antonella
A
Fimiani
Caterina
C
Sirianni
Maria C
MC
Mezzaroma
Ivano
I
Aiuti
Fernando
F
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood; D020395:Receptors, Interleukin-7 / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load
D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7