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/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.
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/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.
Authors: Colleen F Kelley; Christina M R Kitchen; Peter W Hunt; Benigno Rodriguez; Frederick M Hecht; Mari Kitahata; Heide M Crane; James Willig; Michael Mugavero; Michael Saag; Jeffrey N Martin; Steven G Deeks Journal: Clin Infect Dis Date: 2009-03-15 Impact factor: 9.079
Authors: Amanda Leone; Mukta Rohankhedkar; Afam Okoye; Alfred Legasse; Michael K Axthelm; Francois Villinger; Michael Piatak; Jeffrey D Lifson; Brigitte Assouline; Michel Morre; Louis J Picker; Donald L Sodora Journal: J Immunol Date: 2010-07-09 Impact factor: 5.422
Authors: Carey L Shive; Joseph C Mudd; Nicholas T Funderburg; Scott F Sieg; Benjamin Kyi; Doug A Bazdar; Davide Mangioni; Andrea Gori; Jeffrey M Jacobson; Ari D Brooks; Jeffrey Hardacre; John Ammori; Jacob D Estes; Timothy W Schacker; Benigno Rodriguez; Michael M Lederman Journal: J Infect Dis Date: 2014-02-28 Impact factor: 5.226
Authors: B O Taiwo; X Li; F Palella; L P Jacobson; J B Margolick; R Detels; C R Rinaldo; J P Phair Journal: HIV Med Date: 2009-07-09 Impact factor: 3.180
Authors: J Saison; T Ferry; J Demaret; D Maucort Boulch; F Venet; T Perpoint; F Ader; V Icard; C Chidiac; G Monneret Journal: Clin Exp Immunol Date: 2014-06 Impact factor: 4.330