TY - JOUR
T1 - 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
AU - Sojka, Dorothy K.
AU - La Motte, Ross N.
AU - Mokyr, Margalit B.
N1 - Funding Information:
Acknowledgements We would like to thank Dr. Jeffrey Bluestone for helpful discussions and for critically reviewing of this manuscript. This work was supported by research grant CA-76532 from the National Cancer Institute. The contribution of R.N.L.M. was in partial fulfillment of the requirements for the Doctor of Philosophy Degree.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - CTL activity
KW - Chemotherapy-induced immunopotentiation
KW - Costimulatory molecules
UR - http://www.scopus.com/inward/record.url?scp=0033917007&partnerID=8YFLogxK
U2 - 10.1007/s002620050022
DO - 10.1007/s002620050022
M3 - Article
C2 - 10782862
AN - SCOPUS:0033917007
SN - 0340-7004
VL - 49
SP - 10
EP - 22
JO - Cancer Immunology Immunotherapy
JF - Cancer Immunology Immunotherapy
IS - 1
ER -