Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells
J. Clin. Invest. Paolo Monti, et al. 118:1806 doi:10.1172/JCI35197 [Go to this article.]

Figure 5
Expansion of autoreactive T cell clones during homeostatic proliferation. (A) Direct labeling of cells from 5 patients and 1 control subject with PE-labeled HLA-A*0201–GAD65_114–122 pentamers (pmr) and Ki-67 (gated on CD8⁺ cells). Numbers denote percentage of cells in the respective quadrants. Pentamer-positive cells were enriched in the Ki-67⁺ cell population. Direct labeling was also shown using HLA-A*0201–influenza A matrix protein_58–66 (FLU) pentamers as a positive control and HLA-A*0201–HIV-1 gag p17_76–84 pentamers as a negative control. (B) Sequential quantification of autoreactive HLA-A*0201–GAD65_114–122⁺CD8⁺ T cells in patient hSR-055-ITA-Ed06, who was strongly positive for GAD autoantibodies at the time of islet transplantation. The percentage of positive cells (region denoted R3) after in vitro culture increased progressively following transplantation, as shown. The patient ceased taking immunosuppressive therapy at day 56 after transplant as a result of graft failure. (C) In vitro expansion of HLA-A*0201–GAD65_114–122⁺CD45RO⁺CD8⁺ cells from patient hSR-055-ITA-Ed06 taken before transplant by culture with cognate peptide GAD65_114–122 plus IL-7. The percentage of pentamer-positive cells in the upper right quadrant is indicated. The same experiment was also performed using cells from a nondiabetic control subject.