High frequency of regulatory T cells among HIV type 1-infected men who have sex with men correlates with disease progression.

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.

CONCLUSION

Increased proportions and decreased numbers of CD4(+) Tregs are associated with HIV progression, and their functions may impair with the progression of HIV infection.