TY - JOUR
T1 - B7.1 costimulation increases T-cell proliferation and cytotoxicity via selective expansion of specific variable alpha and beta genes of the T-cell receptor
AU - Chan, Allen K.
AU - Goedegebuure, Peter S.
AU - Von Bernstorff, Wolfram
AU - Carritte, Amanda L.
AU - Chung, Min
AU - Stewart, Robyn A.
AU - Montgomery, Leslie
AU - Spanjaard, Remco A.
AU - McKenzie, Allison B.
AU - Eberlein, Timothy J.
PY - 2000
Y1 - 2000
N2 - Background. Optimal T-cell activation requires not only ligation of the T-cell receptor (TcR) but also delivery of costimulatory signals by various accessory molecules. The interaction of the costimulatory molecule B7.1 (CD80) with its receptor CD28 provides a strong positive signal to T cells. Methods. The B7.1 gene was transduced into cultured human ovarian, breast, and pancreatic tumor cells by using a retrovital vector. Autologous as well as allogeneic naive T-cells were stimulated with either wild-type or B7.1- transduced tumor cells in a mixed lymphocyte tumor cell culture (MLTC). In addition to cytolytic activity, T-cell proliferation, T-cell subset composition, and the frequencies of TcR variable (V) alpha and beta genes were compared in T cells from both types of MLTC. Results. Introduction of the B7.1 gene into tumor cells was successful in all tumors to a varying degree. Those tumors expressing high levels of B7.1 induced significantly higher levels of T-cell proliferation than wild-type tumor cells. T-cell subset composition did not markedly differ between T cells stimulated with wild-type tumor cells or B7.1-expressing tumor cells. However, T cells stimulated with B7.1-expressing tumor cells showed a significantly increased cytolytic potential. The increased cytotoxic T lymphocyte activity was associated with a higher frequency of specific TcR Vα and Vβ genes. In addition, B7.1 costimulation promoted oligoclonality among the responding T cells. Conclusions. These data suggest that costimulation through B7.1 promotes T-cell proliferation and cytotoxic activity through clonal expansions of T cells bearing antigen-specific TcR Vα and Vβ genes and through promotion of oligoclonality. The data also suggest that promoting B7.1-mediated costimulation is an important aspect of immune therapies.
AB - Background. Optimal T-cell activation requires not only ligation of the T-cell receptor (TcR) but also delivery of costimulatory signals by various accessory molecules. The interaction of the costimulatory molecule B7.1 (CD80) with its receptor CD28 provides a strong positive signal to T cells. Methods. The B7.1 gene was transduced into cultured human ovarian, breast, and pancreatic tumor cells by using a retrovital vector. Autologous as well as allogeneic naive T-cells were stimulated with either wild-type or B7.1- transduced tumor cells in a mixed lymphocyte tumor cell culture (MLTC). In addition to cytolytic activity, T-cell proliferation, T-cell subset composition, and the frequencies of TcR variable (V) alpha and beta genes were compared in T cells from both types of MLTC. Results. Introduction of the B7.1 gene into tumor cells was successful in all tumors to a varying degree. Those tumors expressing high levels of B7.1 induced significantly higher levels of T-cell proliferation than wild-type tumor cells. T-cell subset composition did not markedly differ between T cells stimulated with wild-type tumor cells or B7.1-expressing tumor cells. However, T cells stimulated with B7.1-expressing tumor cells showed a significantly increased cytolytic potential. The increased cytotoxic T lymphocyte activity was associated with a higher frequency of specific TcR Vα and Vβ genes. In addition, B7.1 costimulation promoted oligoclonality among the responding T cells. Conclusions. These data suggest that costimulation through B7.1 promotes T-cell proliferation and cytotoxic activity through clonal expansions of T cells bearing antigen-specific TcR Vα and Vβ genes and through promotion of oligoclonality. The data also suggest that promoting B7.1-mediated costimulation is an important aspect of immune therapies.
UR - http://www.scopus.com/inward/record.url?scp=0034006444&partnerID=8YFLogxK
U2 - 10.1067/msy.2000.104363
DO - 10.1067/msy.2000.104363
M3 - Article
C2 - 10715992
AN - SCOPUS:0034006444
VL - 127
SP - 342
EP - 350
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 3
ER -