Abstract | INTRODUCTION: METHODS: EAM was induced in A/J, BALB/c, and IL6KO BALB/c male mice by injection of the myocarditogenic peptide in CFA, IFA, or TMax on days 0 and 7. EAM severity was analyzed by histology on day 21. In addition, specific flow cytometry outcomes were evaluated on day 21. RESULTS: Only mice immunized with CFA and myocarditogenic peptide on both days 0 and 7 developed substantial myocarditis as measured by histology. We observed a significantly increased level of IL6 in the spleen 3 days after CFA immunization. In the spleen and heart on day 21, there was an expansion of myeloid cells in CFA-immunized mice, as compared to IFA or TMax-immunized animals. Recombinant IL-6 at the time of IFA immunization partially restored susceptibility of the mice to EAM. We also treated EAM-resistant IL-6 knockout mice with recombinant IL-6 around the time of the first immunization, on days -1 to 2, completely restoring disease susceptibility, showing that the requirement for IL-6 coincides with primary immunization. Examining APC populations in the lymph node draining the immunization site evidenced the contribution of IL-6 to the CFA-dependence of EAM was through controlling local dendritic cell (DC) trafficking. CONCLUSIONS: CFA used with myocarditogenic peptide twice is required to induce EAM in both A/J and Balb/c mice. Although IFA and TiterMax induce antibody responses, only CFA preferentially induced autoantigen-specific responses. CFA expands monocytes in the heart and in the spleen. IL-6 signaling is required during short window around primary immunization to induce EAM. In addition, IL-6 deficient mice resistance to EAM could be reversed by injecting IL-6 around first immunization. IL-6 expands dendritic cell and monocytic populations and ultimately leads to a robust T-cell driven immune response in CFA immunized mice.
|
Authors | Jillian A Fontes, Jobert G Barin, Monica V Talor, Natalie Stickel, Julie Schaub, Noel R Rose, Daniela Čiháková |
Journal | Immunity, inflammation and disease
(Immun Inflamm Dis)
Vol. 5
Issue 2
Pg. 163-176
(06 2017)
ISSN: 2050-4527 [Electronic] England |
PMID | 28474508
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. |
Chemical References |
- Interleukin-6
- interleukin-6, mouse
- Freund's Adjuvant
|
Topics |
- Animals
- Autoimmune Diseases
(chemically induced, genetics, immunology, pathology)
- Freund's Adjuvant
(adverse effects, pharmacology)
- Interleukin-6
(genetics, immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Myocarditis
(chemically induced, genetics, immunology, pathology)
|