Fast-tracked CTL: rapid induction of potent anti-tumor killer T cells in situ.
Current strategies to elicit cytolytic T cell responses specific for tumor-associated or over-expressed self antigens rely on multiple immunizations and in vitro expansion schemes. Here we report the in vivo induction of activated tumor-specific CD8(+) CTL just 6 days after treatment with the IgM immune modulator B7-DC XAb. Antibody treatment of mice at the time of tumor challenge elicited potent CTL with a specificity that distinguished between MHC-compatible tumors. Remarkably, these effector cells were not generated by the extensive proliferation of naive CTL precursors, though their induction required CD4(+) T cell help and classical B7 costimulatory signals. Tumor targets were recognized and lysed in an MHC-restricted, perforin-dependent manner, indicating that these rapidly induced effectors resemble traditionally defined CTL, despite the finding that strong increases in the expression of the effector/memory marker CD44 and the activation marker CD69 were not elicited. These CTL were induced in animals bearing well-established tumors and resulted in anti-tumor protection, underscoring the therapeutic potential of this type of effector T cell population in cancer patients.
Heckman
Karin L
KL
Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Schenk
Erin L
EL
Radhakrishnan
Suresh
S
Pavelko
Kevin D
KD
Hansen
Michael J
MJ
Pease
Larry R
LR
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018122:B7-1 Antigen; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D052899:Pore Forming Cytotoxic Proteins; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger; D054353:Perforin