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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Milner, Joshua D. Ward, Jerrold M. Paul, William E. Keane-myers, Andrea |
| Description | Author Affiliation: Milner JD ( Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.); |
| Abstract | Lymphopenia and restricted T cell repertoires in humans are often associated with severe eosinophilic disease and a T cell Th2 bias. To examine the pathogenesis of this phenomenon, C57BL/6 Rag2-/- mice received limited (3 x 10(4)) or large (2 x 10(6)) numbers of CD4 T cells. Three to 5 months after transfer, mice that had received 3 x 10(4) T cells, but not those that received 2 x 10(6), developed fulminant macrophage pneumonia with eosinophilia, Ym1 deposition, and methacholine-induced airway hyperresponsiveness, as well as eosinophilic gastritis; esophagitis and other organ damage occurred in some cases. Donor cells were enriched for IL-4, IL-5, and IL-13 producers. When 3 x 10(4) cells were transferred into CD3epsilon-/- hosts, the mice developed strikingly elevated serum IgE. Prior transfer of 3 x 10(5) CD25+ CD4 T cells into Rag2-/- recipients prevented disease upon subsequent transfer of CD25- CD4 T cells, whereas 3 x 10(4) regulatory T cells (Tregs) did not, despite the fact that there were equal total numbers of Tregs in the host at the time of transfer of CD25- CD4 T cells. Limited repertoire complexity of Tregs may lead to a failure to control induction of immunopathologic responses, and limitation in repertoire complexity of conventional cells may be responsible for the Th2 phenotype. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Inflammation Etiology Lymphopenia Immunology Th2 Cells Adoptive Transfer Animals CD4-Positive T-Lymphocytes Transplantation DNA-Binding Proteins Deficiency Genetics Immunoglobulin E Blood Pathology Complications Therapy Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phenotype T-Lymphocytes, Regulatory Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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