LACK OF GRANZYME EXPRESSION IN T-LYMPHOCYTES INDICATES POOR CYTOTOXICT-LYMPHOCYTE ACTIVATION IN HUMAN PAPILLOMAVIRUS-ASSOCIATED CERVICAL CARCINOMAS

Changes in major histocompatibility complex (MHC) class I expression i n neoplastic cells are frequently observed in human papillomavirus typ e 16 (HPV16)-associated cervical carcinomas. In order to investigate w hether this affects cytotoxic T-cell (CTL) activation, 20 HPV16-positi ve cervical carcinomas with variable MHC expression were analyzed immu nohistochemically for the expression of granzyme B and interleukin-2 r eceptor (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 amo unts of CD4(+) and CD8(+) cells were found. Double staining revealed t hat CD3(+) granzyme B+ cells were not detected in 19 out of 20 cervica l lesions, whereas in one carcinoma an occasional cluster of granzyme B+ T cells was observed. Positive controls, including genital warts an d renal allograft rejections, showed granzyme B+ T cells. In agreement with this observation was the extremely low frequency of IL-2R(+) T c ells in the carcinomas tested, while warts contained IL-2R(+) lymphocy tes. The data indicate that cytotoxic (CD8(+)) T cells in cervical car cinomas are not activated, as demonstrated by the lack of granzyme B a nd IL-2R expression in the T cells.