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Immunological tolerance to a defined myelin basic protein antigen administered intrathymically.
J Immunol. 1994 Nov 01; 153(9):3890-8.JI

Abstract

To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.

Authors+Show Affiliations

Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7523508

Citation

Goss, J A., et al. "Immunological Tolerance to a Defined Myelin Basic Protein Antigen Administered Intrathymically." Journal of Immunology (Baltimore, Md. : 1950), vol. 153, no. 9, 1994, pp. 3890-8.
Goss JA, Nakafusa Y, Roland CR, et al. Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. J Immunol. 1994;153(9):3890-8.
Goss, J. A., Nakafusa, Y., Roland, C. R., Hickey, W. F., & Flye, M. W. (1994). Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. Journal of Immunology (Baltimore, Md. : 1950), 153(9), 3890-8.
Goss JA, et al. Immunological Tolerance to a Defined Myelin Basic Protein Antigen Administered Intrathymically. J Immunol. 1994 Nov 1;153(9):3890-8. PubMed PMID: 7523508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. AU - Goss,J A, AU - Nakafusa,Y, AU - Roland,C R, AU - Hickey,W F, AU - Flye,M W, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 3890 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 153 IS - 9 N2 - To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7523508/Immunological_tolerance_to_a_defined_myelin_basic_protein_antigen_administered_intrathymically_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&amp;pmid=7523508 DB - PRIME DP - Unbound Medicine ER -