CD25 Appears Non Essential for Human Peripheral Treg Maintenance In Vivo

Background: IL-2 has been reported to be critical for peripheral T reg survival in mouse models. Here, we examined T reg maintenance in a series of paediatric liver transplant recipients who received basiliximab, a therapeutic anti-CD25 monoclonal antibody. Methodology/Principal Findings: FoxP3 + CD4 T cells were analyzed by flow cytometry before liver grafting and more than 9 months later. We found that in vivo CD25 blockade did not lead to Treg depletion: the proportion of FoxP3 + cells among CD4 T cells and the level of FoxP3 expression were both unchanged. IL-2Rb expression was enhanced in FoxP3 + cells both before and after basiliximab treatment, while the level of IL-2Rc expression was similar in Tregs and non-Tregs. No significant change in the weak or absent expression of IL-7Ra and IL-15Ra expression on FoxP3 + cells was observed. Although the proportion of FoxP3 + cells among CD4 T cells did not vary, food allergies occurred more rapidly after liver grafting in patients who received basiliximab, raising questions as to T reg functionality in vivo in the absence of functional CD25. Conclusions: CD25 appears non essential for human Treg peripheral maintenance in vivo. However, our results rais

Resting Regulatory CD4 T Cells: A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy

BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs) are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging

No significant effect of a blocking anti-CD25 antibody on the proportion of human FoxP3^<b>+</b> CD4 T cells in vivo.

<p>The proportion of CD25⁺FoxP3⁺ (<b>1A</b>), CD25⁻FoxP3⁺ (<b>1B</b>) and total FoxP3⁺ cells (<b>1C</b>) among CD4 T lymphocytes was determined before liver grafting and basiliximab injection, and for more than 9 months thereafter; data are means (curves) and SEM at the different time points. In <b>1D</b>, the FoxP3⁺/FoxP3⁻ and FoxP3^hi/FoxP3⁻ MFI ratios were used to compare the level of intracellular FoxP3 expression (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011784#s3" target="_blank">Methods</a>). Means and SEM are shown. The Mann Whitney test was used for statistical analysis. The number of patients tested at each time point is indicated. Only statistically significant differences are indicated.</p

Human FoxP3^<b>+</b> CD4 T cells express high levels of IL-2 Rβ.

<p>IL-2Rβ (<b>Fig. 2A, 2B</b>), IL-2Rγ (<b>Fig. 2A, 2C</b>), IL-15Rα (<b>Fig. 2A, 2D</b>) and IL-7Rα (<b>Fig. 2A, 2E</b>) expression was analyzed by flow cytometry in FoxP3⁺ and FoxP3⁻ CD4 T cells before liver grafting and basiliximab injection (Figs. 2B to 2E), and at various times thereafter (2B to 2E). Fig. A shows a representative pre-graft staining profile. Figs. 2B to 2E represent the mean (SEM) MFI ratios (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011784#s3" target="_blank">Methods</a>). The Wilcoxon test was used to compare FoxP3⁺ and FoxP3⁻ CD4 T cells. The Mann Whitney test was used to analyze the time course of expression in a given cell subset. Only significant differences are indicated.</p

Strong correlations of anti-viral capsid antigen antibody levels in first-degree relatives from families with Epstein-Barr virus-related lymphomas.

International audienceBACKGROUND: Markers of Epstein-Barr virus (EBV) infection include anti-viral capsid antigen (VCA) immunoglobulin (Ig) G. High anti-VCA titers are associated with EBV-related lymphoproliferation, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). METHODS: Intrafamilial correlations of anti-VCA IgG levels were studied in 3 settings: 127 families recruited through patients with HL in France (population A), 31 families recruited through patients with BL in Uganda (population B), and 74 large families from a general population in Cameroon (population C). Titers were determined by enzyme-linked immunosorbent assay (populations A and C) or by immunofluorescence analysis (population B). RESULTS: In populations A and B, the anti-VCA IgG titers of the relatives of patients with HL or BL increased significantly (P = .01 and P < .001, respectively) with those of the index case patient. In all 3 populations, anti-VCA IgG titers were significantly correlated (P < .001 for A, P = .002 for B, and P < .001 for C) between genetically related individuals (father-offspring, mother-offspring, and sibling-sibling) but not between spouses. Similar results were obtained for population A after adjustment for total IgG levels. In all cases, the pattern of correlations was consistent with a polygenic model, with heritability ranging from 0.32 to 0.48. CONCLUSION: These results provide evidence for the genetic control of anti-VCA IgG titers and pave the way for identification of the loci involved