T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART

• Published in: AIDS (London) Vol. 20; no. 16; pp. 2033 - 2041
• Main Authors: Marziali, Marco, De Santis, Wladimiro, Carello, Rossella, Leti, Wilma, Esposito, Antonella, Isgrò, Antonella, Fimiani, Caterina, Sirianni, Maria C, Mezzaroma, Ivano, Aiuti, Fernando
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24.10.2006
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Female; Flow Cytometry; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1; Homeostasis - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunophenotyping; Infectious diseases; Interleukin-7 - blood; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Receptors, Antigen, T-Cell, alpha-beta - blood; Receptors, Interleukin-7 - blood; T-Lymphocyte Subsets - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Human; Immunopathology; Thymus gland; Treg; Homeostasis; AIDS; CD4 T cells; Immune deficiency; interleukin-7; Immunological method; Infection; Numeration; Virus; Chemotherapy; Treatment; Immunological investigation; Viral disease; T-Lymphocyte; Antiviral; IL-7Rα; Infected cell; HAART
• ISSN: 0269-9370
• DOI: 10.1097/01.aids.0000247588.69438.fd

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 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. 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 (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. 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.