Deregulated stress system in non-obese diabetic lymphocyte.
Lymphopenia-induced homeostatic expansion in non-obese diabetic (NOD) mice may lead to autoimmunity. We demonstrated that NOD lymphocytes are more susceptible to apoptosis than those of non-diabetic C57BL/6 or NOD.H2(h4) mice in vivo and in vitro, which may be an underlying mechanism causing lymphopenia in NOD mice. Gene expression profiling identified a set of genes that are differentially expressed between NOD and B6 mice. Identity of these genes suggested that NOD T cells have a deregulated stress response system, especially heat-shock protein family, making them overly sensitive to apoptosis. Thus, we hypothesize that this strain-specific gene expression profile may confer a liability upon NOD T cells making them more susceptible to apoptosis that may lead to lymphopenia in NOD mice and contribute to development of autoimmunity.
Liu
Z
Z
Department of Medicine, Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Aune
T M
TM
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D018076:DNA, Complementary; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005260:Female; D005720:Gamma Rays; D020869:Gene Expression Profiling; D018869:Heat-Shock Response; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013696:Temperature; D014184:Transplantation, Homologous
D018076:DNA, Complementary