(A) Detection of GrB⁺ lymphocytes is shown. A biopsy specimen of an HD patient with ≥15% GrB⁺ cells, presenting with stage-2 disease who died 45 months later as a result of the disease, is shown. Brown cytoplasmic staining indicates GrB expression. (B) Double-staining for CD8 and GrB is shown. The majority of reactive lymphocytes present in the vicinity of the RS cell in the center are CD8⁺ (brown membranous staining). Black cytoplasmic staining shows that many of these CD8⁺ cells also express GrB. GrB⁺/CD8⁻ cells are not observed. Thus, the large majority of GrB⁺ cells should be considered activated CTLs.