Lack of granzyme expression in T lymphocytes indicates poor cytotoxic T lymphocyte activation in human papillomavirus-associated cervical carcinomas.

Abstract

Changes in major histocompatibility complex (MHC) class I expression in neoplastic cells are frequently observed in human papillomavirus type 16 (HPV16)-associated cervical carcinomas. In order to investigate whether this affects cytotoxic T-cell (CTL) activation, 20 HPV16-positive cervical carcinomas with variable MHC expression were analyzed immunohistochemically for the expression of granzyme B and interleukin-2 receptor (IL-2R). The results revealed that most carcinomas show strong CD3+ T-lymphocyte infiltrates. In nine of these cases CD8+ cells outnumbered the CD4+ cells, whereas in the remaining cases equal amounts of CD4+ and CD8+ cells were found. Double staining revealed that CD3+ granzyme B+ cells were not detected in 19 out of 20 cervical lesions, whereas in one carcinoma an occasional cluster of granzyme B+ T cells was observed. Positive controls, including genital warts and renal allograft rejections, showed granzyme B+ T cells. In agreement with this observation was the extremely low frequency of IL-2R+ T cells in the carcinomas tested, while warts contained IL-2R+ lymphocytes. The data indicate that cytotoxic (CD8+) T cells in cervical carcinomas are not activated, as demonstrated by the lack of granzyme B and IL-2R expression in the T cells.