Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo.
We previously showed that immunization with a combination of TLR and CD40 agonists (combined TLR/CD40 agonist immunization) resulted in an expansion of Ag-specific CD8 T cells exponentially greater than the expansion observed to immunization with either agonist alone. We now show that the mechanism behind this expansion of T cells is the regulated expression of CD70 on dendritic cells. In contrast to previous results in vitro, the expression of CD70 on dendritic cells in vivo requires combined TLR/CD40 stimulation and is not significantly induced by stimulation of either pathway alone. Moreover, the exponential expansion of CD8(+) T cells following combined TLR/CD40 agonist immunization is CD70 dependent. Thus, the transition from innate stimuli (TLRs) to adaptive immunity is controlled by the regulated expression of CD70.
Sanchez
Phillip J
PJ
Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
McWilliams
Jennifer A
JA
Haluszczak
Catherine
C
Yagita
Hideo
H
Kedl
Ross M
RM
D000818:Animals; D053282:CD27 Ligand / Q000235:genetics*; D019013:CD40 Antigens / Q000819:agonists*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000819:agonists*
D053282:CD27 Ligand; D019013:CD40 Antigens; D051193:Toll-Like Receptors