The role of T cell costimulation by CD80 in the initiation and maintenance of the immune response to human leukemia.

:Most human myeloid leukemias express both class I and class II HLA and it has been postulated that leukemia-associated peptides are presented by those molecules. It is possible, however, that leukemia cells escape the immune surveillance by lacking expression of "costimulatory" molecules required for activating the immune response. Human erythroleukemia line (HEL) has been the subject of previous detailed studies demonstrating surface expression of bona fide HLA molecules but inability to stimulate allogeneic response of proliferative or cytolytic T cells. We found that an HLA-DR+ subclone (HEL-DR+) expresses LFA-1, LFA-3, ICAM-1, ICAM-3, but neither CD80 nor CD86 on the surface. Transfection of CD80 cDNA into HEL-DR+ cells induced the allogeneic response of purified T cells from both cord blood and peripheral blood of adult donors, demonstrating that CD80 expression could lead to accessory cell-independent activation of naive T cells. Priming allogeneic peripheral blood T cells by HEL-DR+/CD80+ also lead to generation of cytotoxic T lymphocytes that lysed both HEL-DR+/CD80+ and wild type HEL-DR+ equally well, confirming CD80 expression is required only in the CTL induction phase but not in the CTL effector phase. We established and maintained alloproliferative T cell clones from adult blood by stimulation with the HEL-DR+/CD80+ line. The clones could respond not only to HEL-DR+/CD80+ line but also to the HEL-DR+ line; however, the proliferative response to HEL-DR+/CD80+ was amplified and sustained compared to the short-lived response to wild type HEL-DR+ cells. Therefore, expression of CD80 by HEL-DR+ cells was determinant both to initiate and sustain the T cell response. These experiments support the hypothesis that lack of expression of "costimulatory" molecules for T cells contributes to leukemia escape from immune surveillance, and provide preliminary data for the use of CD80 transfection in the immunotherapy of human leukemia.

Matsumoto K ，Anasetti C 《LEUKEMIA & LYMPHOMA》

Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition.

Costello RT ，Mallet F ，Sainty D ，Maraninchi D ，Gastaut JA ，Olive D ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes.

Mutti L ，Valle MT ，Balbi B ，Orengo AM ，Lazzaro A ，Alciato P ，Gatti E ，Betta PG ，Pozzi E ... -  《-》

Decreased inducible expression of CD80 and CD86 in human monocytes after ultraviolet-B irradiation: its involvement in inactivation of allogenecity.

Fujihara M ，Takahashi TA ，Azuma M ，Ogiso C ，Maekawa TL ，Yagita H ，Okumura K ，Sekiguchi S ... -  《BLOOD》

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.

Melichar B ，Nash MA ，Lenzi R ，Platsoucas CD ，Freedman RS ... -  《-》