Immune responses to b7-negative tumors require host-derived B7-CD28 interaction in lymph nodes

G. Yang, M. T. Mizuno, L. Chen

Research output: Contribution to journalArticlepeer-review


Efficient T cell activation requires two distinct signals derived from MHC-antigen complexes and costimulatory molecules. Lack of costimulatory signal, such as B7-CD28 interaction, might cause T cell unresponsiveness. Immunization by some B7-negative tumors, however, induces CTL-mediated antitumor responses rather than T cell anergy. Treatment with CTLA4Ig, a fusion protein that blocks B7-CD28 interaction, prevented tumor rejection of a sub-tumorigenic dose of mastocytoma P815; 90% mice administrated with CTLA4Ig died of metastatic tumor while only 20% mice injected with control mAb died. Treatment with CTLA4Ig also eliminated anti-P815 CTL responses. Similar results were obtained in melanoma E7C3 model. After injection, P815 cells appeared rapidly in local draining lymph nodes (LN) and immunohistochemistry analysis indicated the constitutive expression of B72 in paracortex of LN, suggesting that draining LN are the likely anatomical location of T cell activation. Injection of mice with a subtumorigenic dose of P815 cells and a Mel-14 mAb, which can selectively inhibit homing of naive lymphocytes into LN, eliminated antitumor immunity; 4 out of 5 mice died of tumor following Mel-14 injection while all 5 mice survived after treatment with control mAb. Treatment by Mel-14 mAb also abolished anti-P815 CTL activity in LN. Our findings thus indicate that B7-positive host cells in LN are critical in the initiation of CTL-mediated immunity against tumor.

Original languageEnglish (US)
JournalFASEB Journal
Issue number6
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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