Fig 7. Teplizumab treatment induces IL-10 production and a population of CCR6+CD4+CD25+Foxp3+ T cells in patients.

(A) Serum cytokine analysis from the treated patients subjects showing increase in systemic IL-10 on the day following full dose teplizumab treatment (* p < 0.05 by paired t-test). (B) Representative FACS plot showing decline of CD4CCR6+ T cells in the peripheral blood during treatment. Day 0 before treatment, Day 14 immediately after treatment, and Day 60 (2 months) after treatment). Data from a single patient, representative of 10 is shown. (C) In teplizumab treated subjects CD4+CCR6+ cells decline in the peripheral blood with treatment (*** p < 0.001) and remain lower after treatment (** p < 0.01 by paired t-test). (D) During treatment there is an increase in the expression of Foxp3 on CD4⁺CD25^hiCCR6⁺ (**p< 0.01). (E) Representative FACS plot showing changes in IL-10 expression among CCR6+ and – cells with gates on CD4+CD25+ cells. The increase in IL-10 production is primarily on the CCR6+ cells. A single subject representative of 7 is shown. Cross hairs were drawn at < 1.5% staining with control Abs. (F) Increased expression of IL-10 by CD4⁺CD25^hiCCR6⁺cells from day 0 to day 14 (*p< 0.01). (G) Increase in the numbers of CD4⁺CD25^hiCCR6⁺Foxp3 cells expressing IL-10 in the peripheral circulation during teplizumab treatment (*p<0.05 by paired t-test of Ln(counts (×10^-6) +1). The cell counts were calculated from the blood counts obtained during the clinical trial.