T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART
M Marziali, W De Santis, R Carello, W Leti, A Esposito… - Aids, 2006 - journals.lww.com
M Marziali, W De Santis, R Carello, W Leti, A Esposito, A Isgrò, C Fimiani, MC Sirianni…
Aids, 2006•journals.lww.comObjective: To investigate the pathogenesis of low CD4 T-cell count in subjects who are
immunological non responders (InR) to HAART. Design: 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/μl; subjects with a CD4 T-cell increase> 20% from baseline and a CD4 cell
count> 200/μl were defined as immunological responders (IR). We performed a …
immunological non responders (InR) to HAART. Design: 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/μl; subjects with a CD4 T-cell increase> 20% from baseline and a CD4 cell
count> 200/μl were defined as immunological responders (IR). We performed a …
Abstract
Objective:
To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART.
Design:
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/μl; subjects with a CD4 T-cell increase> 20% from baseline and a CD4 cell count> 200/μl 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 Vβ repertoire, serum concentration of interleukin (IL)-7, the expression of IL-7Rα on naive and memory CD4 and CD8 T cells, and regulatory T cells (T reg) 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-7Rα in both cell subsets, with an increased serum concentration of IL-7 was observed. Furthermore, an increased immune activation with a reduced T reg frequency and increased number of expansions of Vβ families was observed.
Conclusions:
The reduced expression of IL-7Rα associated with the persistent immune activation and the alteration of T reg frequencies in part explains the low level of CD4 T cells observed in InR.
Lippincott Williams & Wilkins