TLR2 engagement on dendritic cells promotes high frequency effector and memory CD4 T cell responses.
Ligation of TLR by distinct pathogen components provides essential signals for T cell priming, although how individual TLR engagement affects primary and memory T cell responses is not well defined. In this study, we demonstrate distinct effects of TLR2 vs TLR4 engagement on primary and memory CD4 T cell responses due to differential effects on APC. Priming of influenza hemagglutinin (HA)-specific naive CD4 T cells with HA peptide and the TLR2 agonist Pam3CysK in vivo resulted in a high frequency of activated HA-specific CD4 T cells that predominantly produced IL-2 and IL-17, whereas priming with HA peptide and the TLR4 agonist LPS yielded a lower frequency of HA-specific CD4 T cells and predominant IFN-gamma producers. TLR2 agonist priming depended on TLR2 expression by APC, as wild-type CD4 T cells did not expand in response to peptide and Pam3CysK in TLR2-deficient hosts. TLR2-mediated priming also led to an increased frequency of Ag-specific memory CD4 T cells compared with TLR4 priming and mediated enhanced secondary responses to influenza challenge. Our results show that TLR engagement on APC influences both primary and secondary CD4 T cell responses, and suggest that long-term functional capacities of T cells are set by innate signals during early phases of an infection.
Chandran
Smita S
SS
Department of Surgery and Microbiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Verhoeven
David
D
Teijaro
John R
JR
Fenton
Matthew J
MJ
Farber
Donna L
DL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D004285:Dogs; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics
D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4