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CD8 is required during positive selection of CD4-/CD8+ T cells
J C Zúñiga-Pflücker1, L A Jones, D L Longo
1Biological Response Modifiers Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Experimental Medicine
|February 1, 1990
Summary
CD8 molecules are crucial for the development of CD8 T cells. Blocking CD8 interactions prevents the generation of CD8 single-positive T cells, indicating a vital role in T cell selection.
Area of Science:
- Immunology
- T cell biology
- Developmental immunology
Background:
- T cell development requires interactions between T cell receptors (TCRs) and self-Major Histocompatibility Complex (MHC) molecules.
- Previous research indicated CD4 molecule interactions shape the T cell repertoire during thymic maturation.
Purpose of the Study:
- To investigate the role of the CD8 molecule in T cell development in vivo.
- To determine if CD8 interactions are essential for the positive selection of CD8+ T cells.
Main Methods:
- In vivo studies using perinatal thymic organ cultures treated with anti-CD8 monoclonal antibodies (mAbs).
- Utilized intact anti-CD8 mAbs and F(ab')2 fragments to block CD8 function.
- Employed F1 mice with selective allele blocking to differentiate between depletion and selection defects.
Main Results:
- Treatment with intact anti-CD8 mAbs prevented the generation of CD8 single-positive T cells.
- F(ab')2 anti-CD8 mAb fragments produced identical results, showing a lack of CD4-/CD8+ cell generation.
- Selective allele blocking demonstrated that the absence of CD8+ T cells results from a lack of positive selection, not depletion, likely due to deficient CD8-MHC class I interaction.
Conclusions:
- CD8 molecules are vital for the positive selection process during T cell development.
- Effective CD8-MHC class I interaction is essential for generating mature single-positive CD8 T cells.
- These findings highlight the critical role of CD8 in shaping the T cell repertoire.