title: Effect of age on the CD4⁺ T-cell impairment in HIV-infected persons without and with cART.
abstract: BACKGROUND
  Knowledge about HIV infection in older persons is becoming increasingly important. CD4⁺ T cells are essential for protective immunity, but little is known about the effect of age on the CD4⁺ T-cell impairment in HIV infection.
  
  
  METHODS
  Treatment-naive patients aged older than 50 or younger than 40 years were studied for absolute and relative frequencies of CD31⁺ naive and CD31⁻ naive CD4⁺ T cells, central memory, effector memory, and terminally differentiated CD4⁺ T cells, and compared with age-matched controls. In addition, cellular proliferation and cytokine secretion properties were determined. CD4⁺ T-cell reconstitution was analyzed in older and younger patients with <350 or ≥ 350 CD4⁺ T cells per microliter at initiation of combination antiretroviral therapy (cART).
  
  
  RESULTS
  CD4⁺ T cells of older but not younger HIV-infected patients showed age-inappropriate low levels of CD31⁻ naive cells, increased levels of effector memory cells, and enhanced interferonγ and interleukin-17 secretion. Impaired CD4⁺ T-cell composition persisted in patients who initiated cART at <350 CD4⁺ T cells per microliter. In patients with CD4⁺ T cells ≥ 350 per microliter, alterations were less pronounced and were reversible with cART. Compared with age-matched controls, total CD4⁺ T-cell counts did not differ between treated younger and older HIV-infected patients.
  
  
  CONCLUSIONS
  These data demonstrate that aging enhances the CD4⁺ T-cell impairment in HIV-infected persons mainly by a loss of CD31⁻ naive cells, accumulation of effector memory cells, and increased pro-inflammatory effector functions. Age-related changes in CD4⁺ T-cell composition can be prevented by an early initiation of cART.
authors.affiliation: *Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany; and †Ärzteforum Seestraβe, Berlin, Germany (Heiko Karcher is now with Ärzteforum Praxis City Ost, Berlin, Germany; Desiree Kunkel is now with Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Klinikum, Charité-University Medicine Berlin, Berlin, Germany).
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.forename: Diana
authors.initials: D
authors.lastname: Bösel
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Epple
authors.forename: Heiko
authors.initials: H
authors.lastname: Karcher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmidt
authors.forename: Désirée
authors.initials: D
authors.lastname: Kunkel
authors.forename: Anika
authors.initials: A
authors.lastname: Geelhaar-Karsch
authors.forename: Katina
authors.initials: K
authors.lastname: Schinnerling
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1