Regulatory T cells in HIV-infected immunological nonresponders are increased in blood but depleted in lymphoid tissue and predict immunological reconstitution.
BACKGROUND
HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3 cells in lymphoid tissue, and the impact of Tregs on immunological reconstitution was determined.


METHODS
HIV-infected individuals on combination antiretroviral therapy for a minimum of 2 years were included. The study population included 14 immunological nonresponders (INR; CD4 T-cell count <200 cells/μL), 33 intermediate responders (CD4 T-cell count 200-500 cells/μL), 30 responders (CD4 T-cell count >500 cells/μL), and 34 healthy controls. Tregs, Treg subpopulations, and intracellular staining for interleukin 10 in peripheral blood were measured using flow cytometry. Foxp3 cells in lymphoid tissue were evaluated using immunolabeling. The CD4 T-cell count was determined at inclusion and after 1 year of follow-up.


RESULTS
INR displayed high percentage of Tregs and activated Tregs in peripheral blood accompanied by a high percentage of Tregs expressing interleukin 10, whereas numbers of Foxp3 cells in lymphoid tissue were low. In contrast, responders resembled healthy controls. Finally, in INR, high level of Tregs in blood and Foxp3 cells in lymphoid tissue were associated with higher level of immunological reconstitution after 1 year of follow-up.


CONCLUSIONS
In conclusion, altered distribution of Tregs was found in INR. Interestingly, high level of Tregs predicted higher level of immunological reconstitution suggesting a role for Tregs in immunological reconstitution.
*Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; Departments of †Clinical Immunology; ‡Otorhinolaryngology; §Pathology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; ‖Department of Infectious Diseases, Hvidovre Hospital, University Hospital of Copenhagen, Copenhagen, Denmark; and ¶Department of Infectious Diseases, Odense Hospital, University of Southern Denmark, Odense, Denmark.
Julie C
JC
Gaardbo
Hans J
HJ
Hartling
Andreas
A
Ronit
Karoline
K
Springborg
Lise M R
LM
Gjerdrum
Elisabeth
E
Ralfkiær
Kristina
K
Thorsteinsson
Henrik
H
Ullum
Åse B
ÅB
Andersen
Susanne D
SD
Nielsen
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D019380:Anti-HIV Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016753:Interleukin-10