T-cell responses differentiate nonaggregated from tungsten-aggregated rhEPO. (A) PBMCs from healthy donors were primed with TT, and restimulated with TT in the presence of 0, 1, or 10 ppm tungsten pin extracts; data presented as mean ± SEM. (B) T cells from 3 normal HX575-naïve healthy donors were primed with clinical lot A, a batch of heat-stressed HX575, or low-tungsten HX575, and restimulated with clinical lot A or B (red triangles), heat-stressed HX575 (red circles), or low-tungsten HX575 (blue triangles). (C) TCLs reactive with heat-stressed HX575, established from healthy HLA-DRB1*09:01-positive donor 8, were restimulated with clinical lot A or B (red triangles), low-tungsten HX575 (blue triangles), nonstressed HX575 (blue circles), or heat-stressed HX575 (red circles). A specific T-cell response shown as SI was calculated by a ratio of cell proliferation with individual stimuli divided by the cell proliferation with vehicle control. SEM, standard error of the mean.