title: Islet lymphocyte subsets in male and female NOD mice are qualitatively similar but quantitatively distinct.
abstract: Islet-infiltrating lymphocytes of individual male and female non-obese diabetic (NOD) mice were examined with the purpose of determining the differences that lead to a predominance of diabetes in female versus males NOD mice. When normalized for the amount of islet lymphocytes recovered, the infiltrating lymphocytes of female NOD mice were indistinguishable from those of male NOD mice. The only observed difference was that islet inflammation progressed at an increased rate in female compared to male NOD mice. There was no difference in the composition of islet infiltrates in male and female NOD mice. Unexpectedly, the ratio of CD4(+):CD8(+) T cells was tightly controlled in the islets throughout diabetogenesis. The frequency of IL-4(+) CD4(+) T cells started high but quickly fell to 3% of the population that was maintained with increasing inflammation. A significant portion of the CD8(+) T cells were islet-specific glucose-6-phosphatase catalytic subunit-related protein specific in both male and female NOD mice and this population was antigen experienced and increased at high levels of islet inflammation. Surprisingly, a large pool of antigen inexperienced naïve T cells was detected in the islets. We conclude the underlying immunological processes in both male and female NOD mice are similar while the rates differ and the presence of naïve T cell in the islets may contribute to epitope spreading.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA. younge@med.unc.edu
authors.forename: Ellen F
authors.initials: EF
authors.lastname: Young
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hess
authors.forename: Larry W
authors.initials: LW
authors.lastname: Arnold
authors.forename: Roland
authors.initials: R
authors.lastname: Tisch
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Frelinger
mesh_terms: D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000166:cytology / Q000276:immunology; D010195:Pancreatitis / Q000276:immunology; D011506:Proteins / Q000276:immunology; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011506:Proteins; D015847:Interleukin-4; D005952:Glucose-6-Phosphatase; C117983:G6pc2 protein, mouse