title: High frequency of regulatory T cells among HIV type 1-infected men who have sex with men correlates with disease progression.
abstract: BACKGROUND
  Regulatory T cells (Tregs) may play an important role in immunopathology during HIV-1 infection. Transcription factor forkhead box P3 (FoxP3) orchestrates the development of Tregs and is a useful marker to identify this population. Using a FoxP3 phenotype to define Tregs, we investigated the level and phenotype of peripheral blood natural CD4(+)Tregs and assessed the relationship between the frequencies and absolute numbers of CD4(+) Tregs and disease progression among untreated HIV-infected men who have sex with men (HIV(+) MSM) in China.
  
  
  METHODS
  Fifty-two untreated HIV(+) MSM with CD4(+) T-cell counts of ≤ 350 cells/µl or > 350 cells/µl were compared in a cross-sectional study. Twelve age-matched HIV-uninfected MSM and nine patients receiving antiretroviral therapy for at least 1 year were also included. Expression of CD25, CD127, CD45RA, CCR7 and CTLA-4 was assessed on CD4(+) Tregs using polychromatic flow cytometry.
  
  
  RESULTS
  The percentage of CD4(+) Tregs was increased significantly, whereas CD4(+) Tregs expressed less CTLA-4 in HIV(+) MSM compared with controls. CD4(+) Tregs displayed predominantly an effector memory phenotype (CD45RA(-) CCR7(-)), phenotypically distinct from conventional CD4(+) T cells. Moreover, the expansive frequencies of CD4(+) Tregs coincided with lower CD4(+) T-cell counts and higher viral loads whereas the absolute numbers of CD4(+) Tregs were associated with higher CD4(+) T-cell counts and lower viral loads. The expansion of Tregs was also associated with CD8(+) T-cell activation.
  
  
  CONCLUSIONS
  Increased proportions and decreased numbers of CD4(+) Tregs are associated with HIV progression, and their functions may impair with the progression of HIV infection.
authors.affiliation: Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wan-hai
authors.initials: WH
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Ming
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Quan-cheng
authors.initials: QC
authors.lastname: Kan
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D018791:CD4 Lymphocyte Count; D060908:CTLA-4 Antigen / Q000032:analysis; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015497:HIV-1; D018451:Homosexuality, Male; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; D012367:RNA, Viral