Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion
Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2003-01-01
|
| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1080/10446670310001626508 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849408328115945472 |
|---|---|
| author | Herman Groen Flip Klatter Jennie Pater Paul Nieuwenhuis Jan Rozing |
| author_facet | Herman Groen Flip Klatter Jennie Pater Paul Nieuwenhuis Jan Rozing |
| author_sort | Herman Groen |
| collection | DOAJ |
| description | Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx) was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1+ recent thymic migrant (RTM) T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8+ and CD45RC+ T cells, whereas the relative loss of RT6+ T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8+ T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8+ T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats. |
| format | Article |
| id | doaj-art-7ebab6cbde104083866edeeebc497036 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2003-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-7ebab6cbde104083866edeeebc4970362025-08-20T03:35:48ZengWileyClinical and Developmental Immunology1740-25221740-25302003-01-01102-414115110.1080/10446670310001626508Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 DepletionHerman Groen0Flip Klatter1Jennie Pater2Paul Nieuwenhuis3Jan Rozing4Department of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, Groningen, The NetherlandsDepartment of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, Groningen, The NetherlandsDepartment of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, Groningen, The NetherlandsDepartment of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, Groningen, The NetherlandsDepartment of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, Groningen, The NetherlandsAutoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx) was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1+ recent thymic migrant (RTM) T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8+ and CD45RC+ T cells, whereas the relative loss of RT6+ T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8+ T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8+ T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats.http://dx.doi.org/10.1080/10446670310001626508 |
| spellingShingle | Herman Groen Flip Klatter Jennie Pater Paul Nieuwenhuis Jan Rozing Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion Clinical and Developmental Immunology |
| title | Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion |
| title_full | Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion |
| title_fullStr | Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion |
| title_full_unstemmed | Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion |
| title_short | Temporary, but Essential Requirement of CD8+ T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion |
| title_sort | temporary but essential requirement of cd8 t cells early in the pathogenesis of diabetes in bb rats as revealed by thymectomy and cd8 depletion |
| url | http://dx.doi.org/10.1080/10446670310001626508 |
| work_keys_str_mv | AT hermangroen temporarybutessentialrequirementofcd8tcellsearlyinthepathogenesisofdiabetesinbbratsasrevealedbythymectomyandcd8depletion AT flipklatter temporarybutessentialrequirementofcd8tcellsearlyinthepathogenesisofdiabetesinbbratsasrevealedbythymectomyandcd8depletion AT jenniepater temporarybutessentialrequirementofcd8tcellsearlyinthepathogenesisofdiabetesinbbratsasrevealedbythymectomyandcd8depletion AT paulnieuwenhuis temporarybutessentialrequirementofcd8tcellsearlyinthepathogenesisofdiabetesinbbratsasrevealedbythymectomyandcd8depletion AT janrozing temporarybutessentialrequirementofcd8tcellsearlyinthepathogenesisofdiabetesinbbratsasrevealedbythymectomyandcd8depletion |