Regulatory T Cells in HIV-Infected Immunological Nonresponders Are Increased in Blood but Depleted in Lymphoid Tissue and Predict Immunological Reconstitution

TY - JOUR

T1 - Regulatory T Cells in HIV-Infected Immunological Nonresponders Are Increased in Blood but Depleted in Lymphoid Tissue and Predict Immunological Reconstitution

AU - Gaardbo, Julie C

AU - Hartling, Hans J

AU - Ronit, Andreas

AU - Springborg, Karoline

AU - Gjerdrum, Lise M R

AU - Ralfkiær, Elisabeth

AU - Thorsteinsson, Kristina

AU - Ullum, Henrik

AU - Andersen, Åse B

AU - Nielsen, Susanne D

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Anti-HIV Agents

KW - CD4 Lymphocyte Count

KW - Case-Control Studies

KW - Female

KW - Forkhead Transcription Factors

KW - Gene Expression Regulation

KW - HIV Infections

KW - Humans

KW - Interleukin-10

KW - Lymphoid Tissue

KW - Male

KW - Middle Aged

KW - T-Lymphocytes, Regulatory

U2 - 10.1097/qai.0000000000000173

DO - 10.1097/qai.0000000000000173

M3 - Journal article

C2 - 24784764

SN - 1525-4135

VL - 66

SP - 349

EP - 357

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

IS - 4

ER -