| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
Division of Endocrinology and Diabetes, Ulm University, Ulm, Germany; and
Alexion Pharmaceuticals, Cheshire, CT 06410
Administration of autoantigens under conditions that induce type 2 immunity frequently leads to protection from T cell-mediated autoimmune diseases. Such treatments, however, are inherently linked to the induction of IgG1 Abs and to the risk of triggering anaphylactic reactions. We studied the therapeutic benefit vs risk of immune deviation in experimental allergic encephalomyelitis of SJL mice induced by MP4, a myelin basic protein-proteolipid protein (PLP) fusion protein. MP4 administration in IFA induced type 2 T cell immunity, IgG1 Abs, and experimental allergic encephalomyelitis protection, and all three were enhanced by repeat injections. Despite high Ab titers, anaphylactic side reactions were not observed when MP4 was repeatedly injected in IFA or as soluble Ag s.c. In contrast, lethal anaphylaxis was seen after s.c. injection of soluble PLP:139–151 peptide, but not when the peptide was reinjected in IFA. Therefore, the Ab response accompanying the immune therapy constituted an anaphylactic risk factor only when the autoantigen was not retained in an adjuvant and when it was small enough to be readily disseminated within the body. Taken together, our data show that treatment regimens can be designed to boost the protective type 2 T cell response while avoiding the risk of Ab-mediated allergic side effects.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institute of Health Grants NS-39434 (to P.V.L.) and AI-47756 (to M.T.-L.). F.S.L. and S.K. were supported by a fellowship from the Studienstiftung des Deutschen Volkes. B.O.B. and F.S.L. were supported by the Deutsche Forschungsgemeinschaft Grant GRK 1041, Molecular Diabetology and Endocrinology in Medicine.
2 Address correspondence and reprint requests to Dr. Paul V. Lehmann, Department of Pathology, Case Western Reserve University School of Medicine, Iris S. and Bert L. Wolstein Research Building, Room 5129, 2103 Cornell Road, Cleveland, OH 44106. E-mail address: pvl2{at}po.cwru.edu
3 Abbreviations used in this paper: MBP, myelin basic protein; PLP, proteolipid protein; MS, multiple sclerosis; PTX, pertussis toxin; HEL, hen egg lysozyme; drLN, draining lymph node; Thpp, T helper-primed precursor.
This article has been cited by other articles:
|
|
 |
|
  S. Scabeni, M. Lapilla, S. Musio, B. Gallo, E. Ciusani, L. Steinman, R. Mantegazza, and R. Pedotti CD4+CD25+ Regulatory T Cells Specific for a Thymus-Expressed Antigen Prevent the Development of Anaphylaxis to Self J. Immunol., April 1, 2008; 180(7): 4433 - 4440. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
