Rotavirus acceleration of murine type 1 diabetes is associated with increased MHC class I-restricted antigen presentation by B cells and elevated proinflammatory cytokine expression by T cells.
Rotavirus infection has been proposed to enhance progression towards type 1 diabetes in at-risk children. Rhesus monkey rotavirus (RRV) accelerates diabetes onset in non-obese diabetic (NOD) and T cell receptor transgenic NOD8.3 mice. Infected NOD mice show virus spread to pancreatic lymph nodes (PLN) and mesenteric lymph nodes (MLN), induction of a serum T helper 1-biased specific antibody response and proinflammatory cytokine mRNA expression in PLN and islets. Here, we analysed the effects of RRV infection on intestinal responses and the activation of antigen presenting cells (APC), T cells and B cells in PLN, MLN, spleen and islets. Diabetes acceleration by RRV was associated with minimal immune activation in Peyer's patches. Increased proinflammatory cytokine expression by APC, including dendritic cells, was observed exclusively in the PLN, while cytokine expression by T cells was detected in islets, PLN, MLN and spleen. RRV infection of NOD8.3 mice increased IFNγ expression by CD8(+) T cells, which primarily recognise an islet autoantigen. A peptide corresponding to RRV VP7 amino acids 5-13, with sequence similarity to this islet autoantigen, did not induce activation or proliferation of NOD8.3 mouse T cells. RRV infection of NOD mice elevated B cell MHC I expression in PLN and MLN, and increased the B cell-mediated proliferation of islet antigen-specific CD8(+) T cells. These studies demonstrate that RRV infection of NOD mice activates APC, T cells and B cells at sites where autoreactive lymphocytes accumulate, in association with proinflammatory cytokine expression and an increased capacity to present antigen. Taken together with previous findings, these data support a possible role for bystander activation in type 1 diabetes acceleration by RRV.
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Jessica A
JA
Pane
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Nicole L
NL
Webster
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Christel
C
Zufferey
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: barbarac@unimelb.edu.au.
Barbara S
BS
Coulson
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D005260:Female; D005805:Genes, MHC Class I; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012401:Rotavirus / Q000276:immunology / Q000502:physiology*; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation
D016207:Cytokines
B cell antigen presentation; IGRP autoantigen; Lymphocyte activation; MLN; Non-obese diabetic (NOD) mice; PLN; RRV; Rotavirus; T cell receptor transgenic NOD mice; cytokine expression; mesenteric lymph nodes; pancreatic lymph nodes; rhesus monkey rotavirus