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Frequency and phenotype of CD4+ FoxP3+ T regulatory cells is associated with disease progression in HIV-1 infected patients
Adriana Thomssen1, Philipp Hartjen1, Sandra Hertling1, Olaf Degen1, Stefan Schmiedel1, Dirk Meyer-Olsen2, Ansgar Lohse1, Joachim Hauber3, Jan van Lunze
Background: There is increasing evidence that regulatory CD4+ T cells (Tregs) are of clinical relevance for the coordination of HIV-specific cellular immune responses. Until now Tregs have only been sub-optimally defined by their co-expression of CD4+ and CD25high. Hence, there are conflicting data about the frequency of Tregs in HIV. Intracellular FoxP3 expression (as well as surface labeling of CD127 and CD25) was recently described as more definitive markers to identify Tregs, but this has not been tested rigorously.
Methods: A multicolor flow panel was developed to determine the frequency and phenotype of Tregs, defined as CD4+, CD25+, FoxP3+ cells. PBMC of a large cohort of 100 HIV-1 infected patients at different stages of immune deficiency were analyzed. The phenotype of these Treg populations using a selection of differentiation markers (CD127, CD39, CCR5, CTLA4 and ICOS). In addition, functional properties of Tregs were tested for selected patients in order to define their inhibitory role.
Results: Overall we saw significantly increased frequencies of Tregs in the HIV+ cohort in comparison to a healthy control group. Additionally the frequency of Tregs increased with higher HIV VL (p < 0.0004), while it was inversely proportional to the CD4+ count (p < 0.0021). CD25high, CD127- expression alone proved to be sufficient to label the Treg population. Patients with undetectable VL either through spontaneous control or antiviral therapy had a significantly lower frequency of Treg cells (p < 0.0309).
Conclusions: Higher frequencies of Tregs were detected in patients with progressive HIV disease. These cells might balance cellular activation of CTL driven by viral replication. It remains to be elucidated whether therapeutic depletion of Treg cells at later stages of HIV infection could actually enhance HIV specific cellular immunity.
Datei SOEDAK_09_OSC4.pdf