UNIGE document Scientific Article
previous document  unige:8944  next document
add to browser collection
Title

Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha

Authors
Ohashi, P. S.
Oehen, S.
Aichele, P.
Pircher, H.
Odermatt, B.
Higuchi, Y.
Buerki, K.
show hidden authors show all authors [1 - 10]
Published in Journal of Immunology. 1993, vol. 150, no. 11, p. 5185-5194
Abstract To study self reactivity, a transgenic mouse model has been established in which the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) is expressed in the beta-islet cells of the pancreas (rat insulin promoter (RIP)-gp). These mice (H-2b) do not spontaneously develop diabetes; however, infection with the LCMV strain WE rapidly induces hyperglycemia. In this study, comparative analysis of H-2k RIP-gp-transgenic animals demonstrated that the haplotype influences the incidence and kinetics of diabetes and alters the requirement for the CD4+ T cell subset. This study also showed that the properties of the virus expressing the self target Ag determined whether hyperglycemia occurred in RIP-gp-transgenic mice. Various LCMV strains were able to induce diabetes in RIP-gp-transgenic animals, whereas infection with a recombinant vaccinia virus expressing LCMV-gp (vacc-gp) did not induce diabetes. However, vacc-gp could induce diabetes in double (RIP-gp/TCR)-transgenic mice, where the majority of CD8+ T cells expressed a receptor specific for LCMV-gp, suggesting that a critical number of self-reactive T cells must be activated to induce disease. Notably, histologic analysis of pancreata taken various days after LCMV or vacc-gp infections indicated that induction of diabetes coincided with an increase in MHC class I expression on the islets of Langerhans. Additional studies with vacc-gp were done to determine other factors that possibly enhance autoimmune attack. Transgenic mice expressing both LCMV-gp and TNF-alpha under the control of the RIP were infected with vacc-gp, and 50% of RIP-gp/TNF-alpha-transgenic animals became hyperglycemic. These data suggest that the increased local lymphocyte traffic as a result of TNF-alpha expression attracts activated gp-specific T cells, enhancing the possibility of hyperglycemia. Collectively, these results demonstrate that the induction of diabetes in this model is influenced by the MHC haplotype, the infectious agent, TNF-alpha expression, the level of MHC class I expression, and the induction of a threshold number of self-reactive CTL.
Keywords AnimalsAntigens, Viral/analysisBase SequenceDiabetes Mellitus, Experimental/ etiology/genetics/immunologyDisease SusceptibilityGlycoproteins/geneticsHaplotypesHistocompatibility Antigens Class I/analysis/ physiologyLymphocytic Choriomeningitis/complications/ immunologyMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataRatsT-Lymphocytes, Helper-Inducer/physiologyTumor Necrosis Factor-alpha/analysis/ physiologyVaccinia virus/immunology
Identifiers
PMID: 8496610
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.jimmunol.org/cgi/reprint/150/11/5185.pdf
Structures
Citation
(ISO format)
OHASHI, P. S. et al. Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha. In: Journal of Immunology, 1993, vol. 150, n° 11, p. 5185-5194. https://archive-ouverte.unige.ch/unige:8944

155 hits

0 download

Update

Deposited on : 2010-07-12

Export document
Format :
Citation style :