Autoantigen immunization at different sites reveals a role for anti-inflammatory effects of IFN-gamma in regulating susceptibility to experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis is induced in B10.PL (H-2(u)) mice by immunization with the immunodominant N-terminal epitope of myelin basic protein, Ac1-9. In the present study, we show that the site of immunization impacts disease incidence and severity. This effect is more marked in female mice than in males. Although immunization in the flanks is effective in eliciting disease, delivery of Ag in the footpad and tailbase results in poor induction. Analyses of the immune responses in female mice following different immunization regimens indicates that resistance to disease is accompanied by higher levels of IFN-gamma and CD11b(+)Gr-1(int) myeloid cells. Such myeloid cells are known to have a suppressive function, and consistent with this knowledge, blockade of IFN-gamma results in increased disease activity and decreased levels of splenic CD11b(+)Gr-1(int) cells. Conversely, injection of adjuvants (CFA or Pam(3)CSK(4)) in the footpad decreases experimental autoimmune encephalomyelitis incidence and severity. Our study indicates that the site of immunization can impact the magnitude of the ensuing inflammatory response, and that at a certain threshold a protective, regulatory circuit can be elicited.
Pastor
Silvia
S
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Minguela
Alfredo
A
Mi
Wentao
W
Ward
E Sally
ES
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D039481:CD11b Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D007113:Immunity, Innate; D015994:Incidence; D018836:Inflammation Mediators / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012720:Severity of Illness Index; D014611:Vaccination / Q000379:methods*
D001324:Autoantigens; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D018836:Inflammation Mediators; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D019707:Receptors, Chemokine; C074815:myelin basic protein 1-9; D007371:Interferon-gamma