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CD2-CD4-CD8- lymph node T lymphocytes in MRL lpr/lpr mice are derived from a CD2+CD4+CD8+ thymic precursor
M M Landolfi1, N Van Houten, J Q Russell
1Department of Medicine, Stanford University Medical School, CA 94305-5487.
Journal of Immunology (Baltimore, Md. : 1950)
|July 15, 1993
Summary
MRL lpr/lpr mice develop autoimmunity due to abnormal T cells. These CD4-CD8- T lymphocytes show demethylation of the CD8 gene, indicating prior CD8 expression during thymic selection.
Area of Science:
- Immunology
- Autoimmunity
- T cell development
Background:
- MRL lpr/lpr mice exhibit age-dependent lymphoproliferation and autoimmunity.
- A hallmark is the accumulation of CD4-CD8- T lymphocytes in lymph nodes.
- These abnormal T cells express B220 and CD44 but lack CD2.
Purpose of the Study:
- To investigate the developmental origin of CD4-CD8- T lymphocytes in MRL lpr/lpr mice.
- To determine if these cells have previously expressed CD8 during thymic selection.
- To clarify the thymic differentiation pathway leading to the abnormal T cell population.
Main Methods:
- Analysis of CD8 gene methylation status in MRL lpr/lpr lymph node cells and thymocytes.
- Demethylation of the CD8 gene was used as a marker for previous CD8 expression.
- Flow cytometry was used to characterize thymocyte populations (B220, CD44, CD2 expression).
Main Results:
- The CD8 gene was found to be demethylated in CD4-CD8- lymph node cells and abnormal thymocytes.
- This demethylation suggests prior expression of CD8 in these cells.
- An increased percentage of atypical B220+, CD44+ thymocytes, expressing CD2, was observed in lpr mice.
Conclusions:
- The data suggest that CD4-CD8- T lymphocytes in MRL lpr/lpr mice arise from a CD4+CD8+ thymic precursor.
- These precursors likely express CD2 and undergo thymic selection, leading to the CD4-CD8- phenotype.
- This provides insight into the aberrant T cell development contributing to autoimmunity in MRL lpr/lpr mice.