Abstract
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 full 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 Iymphocytes (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.
| Original language | English |
|---|---|
| Pages (from-to) | 201-208 |
| Number of pages | 8 |
| Journal | Journal of Leukocyte Biology |
| Volume | 61 |
| Issue number | 2 |
| State | Published - Feb 1 1997 |
| Externally published | Yes |
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Keywords
- CD80
- Cytotoxic T lymphocytes
- gp39
- Transfection
ASJC Scopus subject areas
- Cell Biology
Cite this
CD40-CD40L interactions provide 'third-party' costimulation for T cell response against B7-1-transfected human breast tumor cells. / Pericle, Federica; Epling-Burnette, P. K.; Podack, Eckhard R.; Wei, Sheng; Djeu, Julie Y.
In: Journal of Leukocyte Biology, Vol. 61, No. 2, 01.02.1997, p. 201-208.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD40-CD40L interactions provide 'third-party' costimulation for T cell response against B7-1-transfected human breast tumor cells
AU - Pericle, Federica
AU - Epling-Burnette, P. K.
AU - Podack, Eckhard R.
AU - Wei, Sheng
AU - Djeu, Julie Y.
PY - 1997/2/1
Y1 - 1997/2/1
N2 - 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 full 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 Iymphocytes (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.
AB - 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 full 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 Iymphocytes (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.
KW - CD80
KW - Cytotoxic T lymphocytes
KW - gp39
KW - Transfection
UR - http://www.scopus.com/inward/record.url?scp=0031044729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031044729&partnerID=8YFLogxK
M3 - Article
C2 - 9021926
AN - SCOPUS:0031044729
VL - 61
SP - 201
EP - 208
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -