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
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.