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CD40‐CD40L interactions provide “third‐party” costimulation for T cell response against B7‐1‐transfected human breast tumor cells
Author(s) -
Pericle Federica,
EplingBurnette P. K.,
Podack Eckhard R.,
Wei Sheng,
Djeu Julie Y.
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.61.2.201
Subject(s) - biology , cd40 , transfection , microbiology and biotechnology , breast tumor , cancer research , immunology , cell culture , in vitro , cytotoxic t cell , breast cancer , genetics , cancer
In this study we provide evidence that a human breast carcinoma cell line, MDA‐MB‐231 (MDA), can be made immunogenic following B7 transfection and that fall T cell activation is obtained through cooperation of T‐B lymphocytes via CD40‐CD40L interactions. Tumor cells transfected with either B7 gene (MDAB7), neomycin‐resistant gene only (MDAneo), or untransfected (MDA) were used in an allogeneic mixed lymphocyte tumor culture (MLTC) to investigate their ability to stimulate T cell proliferation and generate cytotoxic T lymphocytes (CTL). MDAB7 induced moderate T cell proliferation while MDAneo or MDA did not. Substantial T cell proliferation and de novo generation of cytolytic T cells was obtained only in response to MDAB7 when B cells were present during the MLTC. CD8 + ‐purified T + B cells proliferated to a greater extent than whole T cell populations + B or CD4 + + B in response to MDAB7. Addition of (α‐B7‐1 or α‐CD40 in the MLTC inhibited T cell proliferation by 65 and 40%, respectively, whereas T cell proliferation and generation of CTL was completely abrogated when MLTC was performed in the presence of both antibodies. These data suggest that the engagement of CD40L on T cells with CD40 on B cells provides a costimulatory signal which, in synergism with TCR‐dependent MDAB7‐T cell recognition (signal 1) and B7/CD28 interactions (signal 2), leads to full T cell activation. J. Leukoc. Biol . 61: 201–208; 1997.