title: Immunosenescence is associated with presence of Kaposi's sarcoma in antiretroviral treated HIV infection.
abstract: OBJECTIVE
  Some antiretroviral treated HIV-infected patients develop Kaposi's sarcoma despite long-term suppression of HIV replication. These Kaposi's sarcoma lesions are consistent with Kaposi's sarcoma observed in the elderly uninfected population ('classical Kaposi's sarcoma'). We investigated potential mechanisms for this phenomenon, focusing on measures of immune activation and T-cell senescence.
  
  
  METHODS
  We compared markers of immunosenescence, naive T cells, activation, and inflammation in CD4+ and CD8+ T cells from antiretroviral-treated participants with new-onset Kaposi's sarcoma (cases, n =  19) and from treated individuals without Kaposi's sarcoma (controls, n  = 47).
  
  
  RESULTS
  There was increased frequency of CD4+ and CD8+ T cells with an immunosenescence phenotype (CD57+ and CD28-) in cases vs. controls (CD4+ T cells: CD57+ 7.4 vs. 3.7%, P = 0.025; CD28- 9.1 vs. 4.8%, P  = 0.025; CD8+ T cells: CD57+ 41.5 vs. 27.7%, P  =  0.003; CD28- 60.5 vs. 51.3%, P  = 0.041). Cases had lower proportions of naïve T cells (CD27+ CD28+ CD45RA+) in CD4+ (23.0 vs. 32.2%, P = 0.023) and CD8+ (11.3 vs. 20.7%, P  <  0.001) T-cell compartments. CCR5 was more highly expressed in CD4+ (16.3 vs. 11.0%, P  = 0.025), and CD8+ (43.1 vs. 28.3%, P < 0.001) T-cell compartments in cases vs. controls. There was no difference in telomere length or telomerase activity in peripheral blood mononuclear cells, or in T-cell expression of activation markers (HLADRCD38).
  
  
  CONCLUSIONS
  Among antiretroviral-treated patients, increased frequencies of T cells with an immunosenescence phenotype and lower frequencies of naive T cells were associated with presence of Kaposi's sarcoma among effectively treated patients. These data suggest that certain immunologic perturbations--including those associated with aging--might be causally associated with development of Kaposi's sarcoma.
authors: Department of Dermatology, University of California, San Francisco, California 94110, USA. Patrick_unemori@yahoo.com
authors: Patrick
authors: P
authors: Unemori
authors: Kieron S
authors: KS
authors: Leslie
authors: Peter W
authors: PW
authors: Hunt
authors: Elizabeth
authors: E
authors: Sinclair
authors: Lorrie
authors: L
authors: Epling
authors: Ronald
authors: R
authors: Mitsuyasu
authors: Rita B
authors: RB
authors: Effros
authors: Jeffrey
authors: J
authors: Dock
authors: Sheila G
authors: SG
authors: Dollard
authors: Steven G
authors: SG
authors: Deeks
authors: Jeffrey N
authors: JN
authors: Martin
authors: Toby A
authors: TA
authors: Maurer
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D016022:Case-Control Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD