Encephalitogenicity of complete Freund's adjuvant relative to CpG is linked to induction of Th17 cells.
For decades, CFA has been the classic adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE). Its encephalitogenic activity has been originally linked to the induction of Th1 responses. CpG, which is also a potent Th1 inducer, has been suggested by some studies to be comparably encephalitogenic. In this study, using the SJL proteolipid protein (PLP) 139-151 peptide EAE model, we show that active immunizations using CFA but not CpG 1826/IFA as an adjuvant induced disease. Passive induction of EAE resulted in severe disease when cells were transferred from PLP in CFA-primed mice but resulted in only a mild, transient disease when cells originated from PLP in CpG 1826/IFA-primed mice. In accordance with these findings, immunizations using CFA but not CpG 1826/IFA as an adjuvant elicited a delayed-type hypersensitivity response. ELISPOT analysis revealed that CFA promoted the differentiation of much higher levels of PLP-specific, IL-17-secreting cells compared with CpG 1826/IFA. Both adjuvants induced comparable frequencies of PLP-specific, IFN-gamma-secreting cells and also induced Ag-specific proliferation to the same extent. The severity of EAE in PLP in CFA-immunized mice was reduced when IL-17 was neutralized in vivo, demonstrating the crucial role of this cytokine in disease induction. The data show that immunizations using the autoantigen in CpG 1826/IFA result in very low frequencies of Ag-specific IL-17 cells, suggesting a lower risk of Th17-mediated pathology when using this adjuvant.
Tigno-Aranjuez
Justine T
JT
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Jaini
Ritika
R
Tuohy
Vincent K
VK
Lehmann
Paul V
PV
Tary-Lehmann
Magdalena
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D018899:CpG Islands / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; C423449:CpG ODN 1826; D020381:Interleukin-17; D007376:Interleukin-2; D018991:Myelin Proteolipid Protein; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma; D004247:DNA; D005620:Freund's Adjuvant