Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Mar 1;183(3):769–776. doi: 10.1084/jem.183.3.769

Does B7-1 expression confer antigen-presenting cell capacity to tumors in vivo?

PMCID: PMC2192347  PMID: 8642281

Abstract

Tumors engineered to express the costimulatory molecule B7-1 can elicit CD8+ cytotoxic T lymphocyte (CTL)-dependent antitumor responses in immunocompetent mice. It has been postulated that this result reflects direct priming of CTL by the modified tumor in vivo. Previous studies of the immune response to a B7-1- murine colon carcinoma expressing influenza nucleoprotein (NP) as a model tumor antigen have demonstrated the crucial role of bone marrow-derived antigen-presenting cells (APCs) in the priming of NP-specific CTL in vivo. In this system, no evidence of direct CTL priming by tumor was detected. We have performed a similar analysis to determine if B7-1 transfectant of this tumor results in the direct priming of CTL, and to compare this response to that primed by host APCs. When H-2b-->H-2bxd bone marrow chimeras were immunized with a single injection of CT26/NP/B7-1 (H-2d), NP-specific CTL were detected that were restricted to the bone marrow haplotype (H- 2b), but not to the tumor haplotype. In contrast, CTL recognizing the NP antigenic epitope in the context of the tumor's major histocompatibility complex were detectable only after multiple immunizations. These results suggest that whereas B7-1+ tumor vaccines result in some degree of direct presentation to CD8+ T cells, the dominant mechanism of CTL priming is through the uptake and presentation of tumor antigens by bone marrow-deprived APCs. However, repeated immunization with B7-1+ tumor cells can efficiently expand the directly primed CD8+ CTL population.

Full Text

The Full Text of this article is available as a PDF (737.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azuma M., Cayabyab M., Buck D., Phillips J. H., Lanier L. L. Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line. J Immunol. 1992 Aug 15;149(4):1115–1123. [PubMed] [Google Scholar]
  2. Azuma M., Cayabyab M., Phillips J. H., Lanier L. L. Requirements for CD28-dependent T cell-mediated cytotoxicity. J Immunol. 1993 Mar 15;150(6):2091–2101. [PubMed] [Google Scholar]
  3. Baskar S., Glimcher L., Nabavi N., Jones R. T., Ostrand-Rosenberg S. Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice. J Exp Med. 1995 Feb 1;181(2):619–629. doi: 10.1084/jem.181.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bevan M. J. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med. 1976 May 1;143(5):1283–1288. doi: 10.1084/jem.143.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevan M. J. Minor H antigens introduced on H-2 different stimulating cells cross-react at the cytotoxic T cell level during in vivo priming. J Immunol. 1976 Dec;117(6):2233–2238. [PubMed] [Google Scholar]
  6. Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
  7. Chen L., McGowan P., Ashe S., Johnston J., Li Y., Hellström I., Hellström K. E. Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med. 1994 Feb 1;179(2):523–532. doi: 10.1084/jem.179.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fetten J. V., Roy N., Gilboa E. A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes. J Immunol. 1991 Oct 15;147(8):2697–2705. [PubMed] [Google Scholar]
  9. Harding F. A., Allison J. P. CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help. J Exp Med. 1993 Jun 1;177(6):1791–1796. doi: 10.1084/jem.177.6.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang A. Y., Golumbek P., Ahmadzadeh M., Jaffee E., Pardoll D., Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 1994 May 13;264(5161):961–965. doi: 10.1126/science.7513904. [DOI] [PubMed] [Google Scholar]
  11. Jenkins M. K., Johnson J. G. Molecules involved in T-cell costimulation. Curr Opin Immunol. 1993 Jun;5(3):361–367. doi: 10.1016/0952-7915(93)90054-v. [DOI] [PubMed] [Google Scholar]
  12. Kündig T. M., Bachmann M. F., DiPaolo C., Simard J. J., Battegay M., Lother H., Gessner A., Kühlcke K., Ohashi P. S., Hengartner H. Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science. 1995 Jun 2;268(5215):1343–1347. doi: 10.1126/science.7761853. [DOI] [PubMed] [Google Scholar]
  13. Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
  14. Nandi D., Gross J. A., Allison J. P. CD28-mediated costimulation is necessary for optimal proliferation of murine NK cells. J Immunol. 1994 Apr 1;152(7):3361–3369. [PubMed] [Google Scholar]
  15. Norton S. D., Hovinen D. E., Jenkins M. K. IL-2 secretion and T cell clonal anergy are induced by distinct biochemical pathways. J Immunol. 1991 Feb 15;146(4):1125–1129. [PubMed] [Google Scholar]
  16. Schwartz R. H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992 Dec 24;71(7):1065–1068. doi: 10.1016/s0092-8674(05)80055-8. [DOI] [PubMed] [Google Scholar]
  17. Shahinian A., Pfeffer K., Lee K. P., Kündig T. M., Kishihara K., Wakeham A., Kawai K., Ohashi P. S., Thompson C. B., Mak T. W. Differential T cell costimulatory requirements in CD28-deficient mice. Science. 1993 Jul 30;261(5121):609–612. doi: 10.1126/science.7688139. [DOI] [PubMed] [Google Scholar]
  18. Tan P., Anasetti C., Hansen J. A., Melrose J., Brunvand M., Bradshaw J., Ledbetter J. A., Linsley P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993 Jan 1;177(1):165–173. doi: 10.1084/jem.177.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Townsend S. E., Allison J. P. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science. 1993 Jan 15;259(5093):368–370. doi: 10.1126/science.7678351. [DOI] [PubMed] [Google Scholar]
  20. Townsend S. E., Su F. W., Atherton J. M., Allison J. P. Specificity and longevity of antitumor immune responses induced by B7-transfected tumors. Cancer Res. 1994 Dec 15;54(24):6477–6483. [PubMed] [Google Scholar]
  21. Yang G., Hellström K. E., Hellström I., Chen L. Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol. 1995 Mar 15;154(6):2794–2800. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES