title: Differential alterations of the CD4 and CD8 T cell subsets in HIV-infected patients on highly active antiretroviral therapy with low CD4 T cell restoration.
abstract: OBJECTIVE
  This study examined the homeostatic parameters possibly related to HIV-infected patients who, despite being under suppressive highly active antiretroviral therapy (HAART), show low-level CD4 T cell repopulation (LLR).
  
  
  METHODS
  Twenty-one LLR individuals, 20 HIV-infected controls with satisfactory CD4 T cell repopulation (R) and 14 healthy subjects were studied. Markers related to activation, senescence and proliferation were analysed for both the CD4 and CD8 T cell subsets. Additionally, soluble CD14 (sCD14) and high-sensitivity C-reactive protein (hsCRP) were measured, and the CD34+ cells and the levels of interleukin-7 (IL-7) receptor were quantified.
  
  
  RESULTS
  The frequency of naive CD4 T cells from LLR patients was significantly reduced, and these cells showed increased expression of markers for activation, senescence and proliferation as compared with naive CD4 T cells from R patients. Naive CD8 T cells were also reduced when compared with those from R patients, but did not exhibit an altered phenotype. Moreover, frequencies of effector memory T cells were higher in LLR than R patients. No differences between LLR and R patients were observed for sCD14 levels, CD34+ cells and the IL-7 receptor, although LLR patients showed a tendency toward increased levels of hsCRP >2 μg/mL.
  
  
  CONCLUSIONS
  Patients with low CD4 T cell restoration under suppressive HAART show significant alterations in T cell homeostasis that do not appear to be related to a reduction in haematopoietic progenitors. sCD14 levels were not specifically altered in these patients. Our results agree with our previously proposed model of premature immunosenescence in LLR patients and further describe homeostatic features associated with poor CD4 recovery.
authors.affiliation: Immunovirology Laboratory (Lab 211) of Institute of Biomedicine of Seville (IBIS), Service of Infectious Diseases, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Méndez-Lagares
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Pergañeda
authors.forename: María
authors.initials: M
authors.lastname: del Mar del Pozo-Balado
authors.forename: Miguel
authors.initials: M
authors.lastname: Genebat
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: María
authors.initials: M
authors.lastname: García García
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Yolanda María
authors.initials: YM
authors.lastname: Pacheco
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018952:Antigens, CD34 / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D002097:C-Reactive Protein / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D020395:Receptors, Interleukin-7; D002097:C-Reactive Protein