B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo

Citation
Xl. Liu et al., B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo, J EXP MED, 194(9), 2001, pp. 1339-1348
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
0022-1007 → ACNP
Volume
194
Issue
9
Year of publication
2001
Pages
1339 - 1348
Database
ISI
SICI code
0022-1007(20011105)194:9<1339:BCCEOA>2.0.ZU;2-B
Abstract
B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulat ory molecules and interacts with inducible costimulatory molecule (ICOS). I ts function for CD8 T cells has not been reported. We report here that expr ession of B7H on the tumor cells reduced tumorigenicity and induced immunit y to subsequent challenge with parental tumor cells. The immune protection correlates with all enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cel ls specific for tumor antigen P1A into mice that bore P1A-expressing tumors . We found that while the transgenic T cells divided faster in mice bearing the B7H(+) tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7-1 and B7-2 oil the endogenous host antigen-presenting c ells (APCs). Interestingly, when B7H(+) and B7H(-) tumors were coinjected, P1CTL selectively eliminated the B7H(+) tumor cells. Moreover, B7H expresse d oil the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large minor burdens . Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/o r H-2L(d), the class I molecule that presents the P1A peptide. Taken togeth er, our results reveal that B7H costimulates clonal expansion of, and cogna te destruction by CD8(+) T lymphocytes in vivo.