B7.1 costimulation increases T-cell proliferation and cytotoxicity via selective expansion of specific variable alpha and beta genes of the T-cell receptor

Allen K. Chan, Peter S. Goedegebuure, Wolfram Von Bernstorff, Amanda L. Carritte, Min Chung, Robyn A. Stewart, Leslie Montgomery, Remco A. Spanjaard, Allison B. McKenzie, Timothy J. Eberlein

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)342-350
Number of pages9
JournalSurgery
Volume127
Issue number3
DOIs
StatePublished - 2000

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