Expression of costimulatory molecules CD80 and CD86 and their receptors CD28, CTLA-4 on malignant ascites CD3(+) tumour-infiltrating lymphocytes (TIL) from patients with ovarian and other types of peritoneal carcinomatosis

Costimulation of T lymphocytes by the leucocyte surface molecules CD80 and CD86 expressed on antigen-presenting cells (APC) is required for the develo pment of T cell responses. The CD28 and CTLA-4 molecules on T cells serve a s receptors for the CD80 and CD86 costimulatory antigens. We have examined the frequency of expression of CD80 (B7.1), CD86 (B7.2), CD28 and CTLA-4 su rface antigens on TIL isolated from malignant ascites or peritoneal washing s of 26 patients with ovarian carcinoma and five patients with non-ovarian peritoneal carcinomatosis. Expression of CD80 and CD86 antigen was detected by reverse transcription-polymerase chain reaction (RT-PCR), and by FACS a nalysis. Significantly higher proportions of intraperitoneal CD3(+) cells e xpressed CD86 antigen than the CD80 antigen (14 +/- 9% versus 3 +/- 3%, P < 0.05). Moreover, CD3(+)CD86(+) cells were significantly more frequent in t he peritoneal fluid (14 +/- 9%) than in the peripheral blood (3 +/- 0.4%, P < 0.05) of ovarian patients or normal controls (3 +/- 1%). CTLA-4 and CD28 antigen were expressed, respectively, on 9 +/- 4% and 86 +/- 14% of asciti c CD3(+) cells of ovarian cancer patients. Both CD80 and CD86 antigens were expressed primarily on HLA-DR+ ascites TIL and were present in a very low proportion of HLA-DR- ascites TIL. These HLA-DR+ cells may represent a popu lation of lymphocytes that have been activated in vivo, and function as APC . An anti-CD86 MoAb or a combination of anti-CD86 and anti-CD80 MoAbs signi ficantly inhibited the proliferation of cultured intraperitoneal TIL. We ha ve shown that in addition to CD28 and CTLA-4, CD3(+) intraperitoneal TIL ex press the costimulatory molecules CD80 and CD86. The expression of these mo lecules on T cells could be dependent upon certain factors in the tumour mi croenvironment that could determine the outcome of in vivo immune responses .