Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease.
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Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease. / Schulze Zur Wiesch, Julian; Thomssen, Adriana; Hartjen, Philip; Toth, Ilona; Lehmann, Clara; Meyer-Olson, Dirk; Colberg, Kristina; Frerk, Sebastian; Babikir, Dalia; Schmiedel, Stefan; Degen, Olaf; Mauss, Stefan; Rockstroh, Jürgen; Staszewski, Schlomo; Khaykin, Pavel; Strasak, Alexander; Lohse, Ansgar W.; Fätkenheuer, Gerd; Hauber, Joachim; van Lunzen, Jan.
In: J VIROL, Vol. 85, No. 3, 3, 2011, p. 1287-1297.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease.
AU - Schulze Zur Wiesch, Julian
AU - Thomssen, Adriana
AU - Hartjen, Philip
AU - Toth, Ilona
AU - Lehmann, Clara
AU - Meyer-Olson, Dirk
AU - Colberg, Kristina
AU - Frerk, Sebastian
AU - Babikir, Dalia
AU - Schmiedel, Stefan
AU - Degen, Olaf
AU - Mauss, Stefan
AU - Rockstroh, Jürgen
AU - Staszewski, Schlomo
AU - Khaykin, Pavel
AU - Strasak, Alexander
AU - Lohse, Ansgar W.
AU - Fätkenheuer, Gerd
AU - Hauber, Joachim
AU - van Lunzen, Jan
PY - 2011
Y1 - 2011
N2 - There are conflicting data about the frequency and role of regulatory T cells (Tregs) during the course of HIV infection. Peripheral blood of a large cohort of HIV-infected patients (n = 131) at different stages of disease, including 15 long-term nonprogressors and 21 elite controllers, was analyzed to determine the frequency and phenotype of Tregs, defined as CD4(+), CD25(high), CD127(low), FoxP3(high) cells. A significantly increased relative frequency of Tregs within the CD4(+) compartment of HIV(+) patients compared to that of healthy controls (P <0.0001) was observed. Additionally, the relative frequency of Tregs directly correlated with HIV viral load and inversely with CD4(+) counts. However, the absolute Treg number was reduced in HIV-infected patients versus healthy controls (P <0.0001), with the exception of elite controllers (P > 0.05). The loss of absolute Treg numbers coincided with rising markers of immune activation (P <0.0006). The initiation of antiviral therapy significantly increased absolute Treg numbers (P <0.0031). We find that the expression of CD39, a newly defined ectonucleotidase with immunomodulatory functions on Tregs, correlated with progressive HIV disease, HIV viral load, and immune activation. Of note, when tested in peripheral blood mononuclear cells of healthy volunteers, the in vitro capacity to suppress T-cell proliferation was limited to CD4(+), CD25(high), CD39(+) T cells. Interestingly, Tregs of elite controllers exhibited not only the highest expression of CCR5, CTLA-4, and ICOS but also the lowest level of CD39. The data presented here reconcile the seemingly contradictory results of previous studies looking at Tregs in HIV and highlight the complexity of Treg-mediated immunoregulation during human viral infections.
AB - There are conflicting data about the frequency and role of regulatory T cells (Tregs) during the course of HIV infection. Peripheral blood of a large cohort of HIV-infected patients (n = 131) at different stages of disease, including 15 long-term nonprogressors and 21 elite controllers, was analyzed to determine the frequency and phenotype of Tregs, defined as CD4(+), CD25(high), CD127(low), FoxP3(high) cells. A significantly increased relative frequency of Tregs within the CD4(+) compartment of HIV(+) patients compared to that of healthy controls (P <0.0001) was observed. Additionally, the relative frequency of Tregs directly correlated with HIV viral load and inversely with CD4(+) counts. However, the absolute Treg number was reduced in HIV-infected patients versus healthy controls (P <0.0001), with the exception of elite controllers (P > 0.05). The loss of absolute Treg numbers coincided with rising markers of immune activation (P <0.0006). The initiation of antiviral therapy significantly increased absolute Treg numbers (P <0.0031). We find that the expression of CD39, a newly defined ectonucleotidase with immunomodulatory functions on Tregs, correlated with progressive HIV disease, HIV viral load, and immune activation. Of note, when tested in peripheral blood mononuclear cells of healthy volunteers, the in vitro capacity to suppress T-cell proliferation was limited to CD4(+), CD25(high), CD39(+) T cells. Interestingly, Tregs of elite controllers exhibited not only the highest expression of CCR5, CTLA-4, and ICOS but also the lowest level of CD39. The data presented here reconcile the seemingly contradictory results of previous studies looking at Tregs in HIV and highlight the complexity of Treg-mediated immunoregulation during human viral infections.
M3 - SCORING: Journal article
VL - 85
SP - 1287
EP - 1297
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 3
M1 - 3
ER -
