B7-2 expression on tumor cells is important for the acquisition of cytotoxic T lymphocyte activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers via a mechanism that requires either B7-1 or B7-2 expression on host antigen-presenting cells.
We have previously shown that B7-2 (CD86) and, to a lesser extent, B7-1 (CD80) contribute to the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor under conditions that lead to the acquisition of potent cytotoxic T lymphocyte (CTL) activity at the tumor site. Since B7-1 and B7-2 are expressed on both tumor cells and host antigen-presenting cells (APC), the current studies were undertaken to examine the relative importance of each costimulatory molecule on tumor cells and on host APC for the acquisition of anti-MOPC-315 CTL activity. Utilizing an in vitro system for the acquisition of CTL activity, we found that B7 expression on host APC is important for the development of CTL activity in stimulation cultures of spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers, although the expression of either B7-1 or B7-2 is sufficient. In addition, we found that B7-2, which is expressed at high levels on stimulator tumor cells, but not B7-1, which is expressed at much lower levels, is also important for the acquisition of CTL activity. However, the vast majority of the CTL activity acquired in vitro in response to stimulation with the B7-2-expressing MOPC-315 tumor cells was found to depend on B7-expressing host APC. Thus, it is likely that B7-2, which is expressed at high levels on MOPC-315 tumor cells, promotes the rapid lysis of MOPC-315 stimulator tumor cells, thereby making tumor-associated antigens more readily available for efficient presentation by B7-expressing host APC which, in turn, stimulate the acquisition of CTL activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers.
Sojka
D K
DK
Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 60612, USA.
La Motte
R N
RN
Mokyr
M B
MB
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D051940:B7-2 Antigen; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D008211:Lymphocyte Cooperation; D008558:Melphalan / Q000008:administration & dosage; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000188:drug therapy / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D008558:Melphalan