1. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART
- Author
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Rossella Carello, Fernando Aiuti, Antonella Isgrò, Wilma Leti, Maria Caterina Sirianni, Ivano Mezzaroma, Wladimiro De Santis, Marco Marziali, Antonella Esposito, and Caterina Fimiani
- Subjects
Adult ,Male ,Receptors, Antigen, T-Cell, alpha-beta ,T cell ,Immunology ,HIV Infections ,Biology ,Peripheral blood mononuclear cell ,Immunophenotyping ,Immune system ,Antigen ,T-Lymphocyte Subsets ,Antiretroviral Therapy, Highly Active ,medicine ,Homeostasis ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Receptors, Interleukin-7 ,Interleukin-7 ,Interleukin ,T lymphocyte ,Middle Aged ,Viral Load ,Flow Cytometry ,CD4 Lymphocyte Count ,Infectious Diseases ,medicine.anatomical_structure ,HIV-1 ,Female ,cd4 t cells ,haart ,il-7r alpha ,il-7rα ,interleukin-7 ,t reg ,t-reg - Abstract
To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART.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 increase20% from CD4 cell baseline or CD4 cell count200/microl; subjects with a CD4 T-cell increase20% from baseline and a CD4 cell count200/microl were defined as immunological responders (IR). We performed a comprehensive study to characterize the immune response of InR.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.In InR a significant reduction (P0.0001) 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.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.
- Published
- 2006