TY - JOUR
T1 - Enhanced CD8 T cell cross-presentation by macrophages with targeted disruption of STAT3
AU - Brayer, Jason
AU - Cheng, Fengdong
AU - Wang, Hongwei
AU - Horna, Pedro
AU - Vicente-Suarez, Ildefonso
AU - Pinilla-Ibarz, Javier
AU - Sotomayor, Eduardo M.
PY - 2010/7
Y1 - 2010/7
N2 - CD8 T cell tolerance, once thought to be largely a result of clonal deletion, is now appreciated to be much more complex, additionally involving multiple permutations of partial loss of effector function in residual clonal populations. This is especially important in the context of tumor immunity, in which persistent tolerized cytotoxic CD8 T cells (CTL), if reactivated, could potentially mount a protective response. Previously we have shown that antigen-presenting cells (APCs) with a targeted disruption of STAT3 break tolerance in CD4 T cells. Here we evaluate the STAT3-defective APC in terms of its ability to induce a productive CTL response. Our data demonstrate that macrophages derived from conditional STAT3 knockout mice are superior to wild-type macrophages in terms of their ability to prime cognate CTL responses, and to cross-present tumor-derived antigen to CTLs in vitro. CTLs cultured with STAT3-deficient APCs demonstrated a stronger proliferative response and produced increased amounts of IFN-γ and TNF-α, all of which have been shown to be diminished in tumor-tolerized CD8 T cells. Targeting STAT3 signaling represents therefore an enticing strategy to augment CTL responses in the tumor-bearing host.
AB - CD8 T cell tolerance, once thought to be largely a result of clonal deletion, is now appreciated to be much more complex, additionally involving multiple permutations of partial loss of effector function in residual clonal populations. This is especially important in the context of tumor immunity, in which persistent tolerized cytotoxic CD8 T cells (CTL), if reactivated, could potentially mount a protective response. Previously we have shown that antigen-presenting cells (APCs) with a targeted disruption of STAT3 break tolerance in CD4 T cells. Here we evaluate the STAT3-defective APC in terms of its ability to induce a productive CTL response. Our data demonstrate that macrophages derived from conditional STAT3 knockout mice are superior to wild-type macrophages in terms of their ability to prime cognate CTL responses, and to cross-present tumor-derived antigen to CTLs in vitro. CTLs cultured with STAT3-deficient APCs demonstrated a stronger proliferative response and produced increased amounts of IFN-γ and TNF-α, all of which have been shown to be diminished in tumor-tolerized CD8 T cells. Targeting STAT3 signaling represents therefore an enticing strategy to augment CTL responses in the tumor-bearing host.
KW - CD8
KW - Cytotoxic
KW - STAT3
UR - http://www.scopus.com/inward/record.url?scp=77953708336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953708336&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2010.03.004
DO - 10.1016/j.imlet.2010.03.004
M3 - Article
C2 - 20346983
AN - SCOPUS:77953708336
SN - 0165-2478
VL - 131
SP - 126
EP - 130
JO - Immunology Letters
JF - Immunology Letters
IS - 2
ER -