CD4 help-independent induction of cytotoxic CD8 cells to allogeneic P815 tumor cells is absolutely dependent on costimulation

Citation
Yf. Zhan et al., CD4 help-independent induction of cytotoxic CD8 cells to allogeneic P815 tumor cells is absolutely dependent on costimulation, J IMMUNOL, 165(7), 2000, pp. 3612-3619
Citations number
55
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
7
Year of publication
2000
Pages
3612 - 3619
Database
ISI
SICI code
0022-1767(20001001)165:7<3612:CHIOCC>2.0.ZU;2-5
Abstract
Mice made transgenic (Tg) for a rat anti-mouse CD4 Ab (GK mice) represent a novel CD4-deficient model. They not only lack canonical CD4 cells in the p eriphery, but also lack the residual aberrant Th cells that are found in CD 4(-/-) mice and MHC class II-/- mice. To analyze the role of CD4 help and c ostimulation for CTL induction against alloantigens, we have assessed the s urface and functional phenotype of CD8 cells in vivo (e.g., clearance of al logeneic P815 cells) and in vitro. In our CD4-deficient GK mice, CTL respon ses to allogeneic P815 cells were induced, albeit delayed, and were suffici ent to eliminate P815 cells. Induction of CTL and elimination of allogeneic P815 cells were inhibited both in the presence and absence of CD4 cells by temporary CD40 ligand blockade. This indicated that direct interaction of CD40/CD40L between APCs and CD8 cells may be an accessory signal in CTL ind uction las well as the indirect pathway via APC/CD4 interaction). Furthermo re, whereas in CTLA4Ig single Tg mice P815 cells were rejected promptly, in the double Tg GK/CTLA4Ig mice CTL were not induced and allogeneic P815 cel ls were not rejected. These findings suggest that CD40/CD40L is involved in both CD4-dependent and CD4-independent pathways, and that B7/CD28 is pivot al in the CD4-independent pathway of CTL induction against allogeneic P815 cells.