Image-Guided Analyses Reveal that Non-CD4 Splenocytes Contribute to CD4 + T Cell–Mediated Inflammation Leading to Islet Destruction by Altering Their Local Function and Not Systemic Trafficking Patterns
| Autor: | Chih-Pin Liu, Mi-Heon Lee, Wen-Hui Lee, Christopher H. Contag, Yanghao Van |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
lcsh:Medical technology Cell Biomedical Engineering CD11c Mice Transgenic Inflammation Biology Islets of Langerhans Mice Cell Movement Mice Inbred NOD Image Processing Computer-Assisted medicine Animals Bioluminescence imaging Radiology Nuclear Medicine and imaging Luciferases lcsh:QH301-705.5 NOD mice geography geography.geographical_feature_category Cell Death Flow Cytometry Condensed Matter Physics medicine.disease Islet Cell biology Luminescent Proteins Diabetes Mellitus Type 1 medicine.anatomical_structure Pancreatitis lcsh:Biology (General) lcsh:R855-855.5 Integrin alpha M CD4 Antigens Immunology biology.protein Molecular Medicine medicine.symptom Insulitis Spleen Biotechnology |
| Zdroj: | Molecular Imaging, Vol 6 (2007) |
| ISSN: | 1536-0121 |
| DOI: | 10.2310/7290.2007.00033 |
| Popis: | Recruitment of CD4(+) T cells into islets is a critical component of islet inflammation (insulitis) leading to type 1 diabetes; therefore, determining if conditions used to treat diabetes change their trafficking patterns is relevant to the outcome. Cotransfer of CD4(+)BDC2.5 (BDC) cells with non-CD4 splenocytes obtained from newly diabetic NOD mice, but not when they are transferred alone, induces accelerated diabetes. It is unclear whether these splenocytes affect diabetes development by altering the systemic and/or local trafficking and proliferation patterns of BDC cells in target and nontarget tissues. To address these questions, we developed an animal model to visualize BDC cell trafficking and proliferation using whole-body in vivo bioluminescence imaging and used the images to direct tissue sampling for further analyses of the cell distribution within tissues. The whole-body, or macroscopic, trafficking patterns were not dramatically altered in both groups of recipient mice. However, the local patterns of cell distribution were distinct, which led to invasive insulitis only in cotransferred mice with an increased number of islet-infiltrating CD11b(+) and CD11c(+) cells. Taken together, the non-CD4 splenocytes act locally by promoting invasive insulitis without altering the systemic trafficking patterns or proliferation of BDC cells and thus contributing to diabetes by altering the localization within the tissue. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|