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Cell adhesion molecules: a selective therapeutic target for alleviation of IDDM.
J Autoimmun. 1994 Dec; 7(6):859-64.JA

Abstract

Selective homing of autoreactive lymphocytes to the pancreatic islets of Langerhans is essential for triggering the cascade of molecular and cellular interactions which culminate in the specific destruction of the insulin-producing beta-cells. Based upon the sequential multistep model of lymphocyte adhesion to the endothelium, we investigated the possibility of preventing the progression of insulin-dependent diabetes mellitus (IDDM) by selectively blocking L-selectin and alpha 4-integrin homing receptors, which function at different stages of the adhesion process. Treatment of NOD mice with mAb specific for L-selectin or alpha 4-integrin resulted in a significant inhibition of lymphocytic infiltration (insulitis). Both spontaneous development and acute transfer of IDDM were completely prevented by administration of anti-alpha 4-integrin antibody and partially inhibited by anti-L-selectin antibody. The protective effect was of long duration. Interestingly, the autoimmune T cell responses to a panel of beta cell autoantigens and the lymphocytic infiltration of salivary glands (sialadenitis) appeared unaffected by anti-L-selectin or anti-alpha 4-integrin treatment. These data suggest that prevention of lymphocyte homing to the pancreatic islets may provide a selective target for prevention/treatment of IDDM in patients.

Authors+Show Affiliations

Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7534080

Citation

Yang, X D., et al. "Cell Adhesion Molecules: a Selective Therapeutic Target for Alleviation of IDDM." Journal of Autoimmunity, vol. 7, no. 6, 1994, pp. 859-64.
Yang XD, Michie SA, Tisch R, et al. Cell adhesion molecules: a selective therapeutic target for alleviation of IDDM. J Autoimmun. 1994;7(6):859-64.
Yang, X. D., Michie, S. A., Tisch, R., Karin, N., Steinman, L., & McDevitt, H. O. (1994). Cell adhesion molecules: a selective therapeutic target for alleviation of IDDM. Journal of Autoimmunity, 7(6), 859-64.
Yang XD, et al. Cell Adhesion Molecules: a Selective Therapeutic Target for Alleviation of IDDM. J Autoimmun. 1994;7(6):859-64. PubMed PMID: 7534080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cell adhesion molecules: a selective therapeutic target for alleviation of IDDM. AU - Yang,X D, AU - Michie,S A, AU - Tisch,R, AU - Karin,N, AU - Steinman,L, AU - McDevitt,H O, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 859 EP - 64 JF - Journal of autoimmunity JO - J Autoimmun VL - 7 IS - 6 N2 - Selective homing of autoreactive lymphocytes to the pancreatic islets of Langerhans is essential for triggering the cascade of molecular and cellular interactions which culminate in the specific destruction of the insulin-producing beta-cells. Based upon the sequential multistep model of lymphocyte adhesion to the endothelium, we investigated the possibility of preventing the progression of insulin-dependent diabetes mellitus (IDDM) by selectively blocking L-selectin and alpha 4-integrin homing receptors, which function at different stages of the adhesion process. Treatment of NOD mice with mAb specific for L-selectin or alpha 4-integrin resulted in a significant inhibition of lymphocytic infiltration (insulitis). Both spontaneous development and acute transfer of IDDM were completely prevented by administration of anti-alpha 4-integrin antibody and partially inhibited by anti-L-selectin antibody. The protective effect was of long duration. Interestingly, the autoimmune T cell responses to a panel of beta cell autoantigens and the lymphocytic infiltration of salivary glands (sialadenitis) appeared unaffected by anti-L-selectin or anti-alpha 4-integrin treatment. These data suggest that prevention of lymphocyte homing to the pancreatic islets may provide a selective target for prevention/treatment of IDDM in patients. SN - 0896-8411 UR - https://www.unboundmedicine.com/medline/citation/7534080/Cell_adhesion_molecules:_a_selective_therapeutic_target_for_alleviation_of_IDDM_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-8411(84)71069-9 DB - PRIME DP - Unbound Medicine ER -