TY - JOUR
T1 - Anaphylaxis to a self-peptide in the absence of mast cells or histamine
AU - Musio, Silvia
AU - Pedotti, Paola
AU - Mantegazza, Renato
AU - Ohtsu, Hiroshi
AU - Boon, Louis
AU - Steinman, Lawrence
AU - Galli, Stephen J.
AU - Pedotti, Rosetta
N1 - Funding Information:
We thank Dennis Mitchell for technical help and Renato Longhi for providing the peptide used in this study. This work was funded by grants from the National MS Society-New York, CARIPLO foundation and ‘Ricerca Finalizzata-Ministero della Salute’ (to RP).
PY - 2009/4
Y1 - 2009/4
N2 - Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (KitWKitW-v mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.
AB - Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (KitWKitW-v mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.
KW - Anaphylaxis
KW - Experimental autoimmune encephalomyelitis
KW - Histamine
KW - IL-4
KW - Mast cells
KW - Self-peptide
UR - http://www.scopus.com/inward/record.url?scp=63449141923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63449141923&partnerID=8YFLogxK
U2 - 10.1038/labinvest.2009.4
DO - 10.1038/labinvest.2009.4
M3 - Article
C2 - 19188909
AN - SCOPUS:63449141923
VL - 89
SP - 398
EP - 405
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 4
ER -