PMC2193107_01
Progression of inflammatory lesions appearing around pigmented areas of skin from days 5-7 after T cell infusion 3.
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Some lesions developed into bullae and underwent a vitiliginous change, whereas others began to spread and coalesce over the next 3 d to cover most of her back and upper arms (Fig. 2).
Immunohistochemical staining of inflammatory lesion from skin biopsy obtained on day 6. Hematoxylin and eosin stain demonstrates intense lymphocytic infiltrate in the dermal-epidermal junction in the area of melanocytic nevus. Immunohistochemical staining of the same section demonstrates a predominant population of CD4-CD8+ lymphocytes in infiltrate.
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Histologically, the skin displayed an intense inflammatory infiltrate composed of lymphocytes centered around the dermal-epidermal junction (Fig. 3).
Characterization of lymphocytes harvested from skin biopsy obtained day 6 after CTL infusion 3 (left) and from tumor biopsy (right). Same skin sample as in Fig. 3. Flow cytometry analysis (left) using PE-conjugated M27 tetramer or an irrelevant (T369) tetramer and anti-CD8-FITC antibody demonstrates a population of MART-1-specific CTL clones representing >28% of the CD8+ lymphocyte population recovered from the skin biopsy. Flow cytometry analysis (right) of tumor biopsy demonstrates MART-1-specific CTL staining comprising >37% of CD8+ lymphocytes in tumor sample.
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Staining of these cells using peptide-MHC tetramers revealed a substantial proportion (28.2%) of CD8+ T cells binding specifically to the M27 peptide-MHC tetramer (Fig. 4). Approximately 38% of CD8+ lymphocytes from this specimen stained with the MART-1 (M27) peptide-MHC tetramer but not with control tetramers (tyrosinase and gp100), demonstrating that infused MART-1-specific T cells localized not only to normal melanocytes in the skin but also to tumor sites (Fig. 4).