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Presence of CD4 and CD8 determinants on CD4-CD8- murine thymocytes: passive acquisition of CD8 accessory molecules
E W Shores1, S O Sharrow, A Singer
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Insights
Thymocytes can acquire CD4 and CD8 accessory molecules from other cells, rather than producing them. This passive acquisition means low-level expression of these molecules doesn't always define distinct thymocyte subsets.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD4 and CD8 are critical accessory molecules for T cell development.
- Thymocyte subpopulations are often defined by the expression of CD4 and CD8.
- The origin of low-level CD4/CD8 expression on certain thymocytes remains unclear.
Purpose of the Study:
- To investigate whether thymocytes can passively acquire CD4 and CD8 accessory molecules.
- To determine if low-level CD4/CD8 expression on double-negative thymocytes results from acquisition.
Main Methods:
- Analysis of CD4 and CD8 expression on thymocytes.
- In vivo and in vitro mixing experiments using thymocytes with different CD8 alleles (Ly-2.1 and Ly-2.2).
Main Results:
- Most CD4-CD8- thymocytes showed low levels of CD4 and CD8.
- Detection of CD4/CD8 on CD4-CD8- cells was dependent on the presence of CD4+/CD8+ cells.
- Thymocytes expressing Ly-2.1 acquired and expressed the Ly-2.2 allele from other cells.
Conclusions:
- Thymocytes can passively acquire cell surface CD8 molecules they do not synthesize.
- Low-level surface expression of CD4/CD8 differentiation molecules may not indicate distinct thymocyte subpopulations.
- This finding challenges traditional definitions of thymocyte subsets based solely on CD4/CD8 expression.
Abstract:
In the present study we have examined the possibility that CD4 and CD8 accessory molecules can be passively acquired by thymocytes. We initially observed that most thymocytes contained within the CD4-CD8- subset actually possess low levels of CD4 and CD8 on their cell surface. However, the detection of CD4 and CD8 on CD4-CD8- cells was dependent on the presence of other CD4+/CD8+ thymocytes which were actively synthesizing CD4 and CD8. These initial findings suggested that the appearance of CD4/CD8 on "double-negative" thymocytes was due to the passive acquisition of these accessory molecules from CD4+/CD8+ cells present within the thymus. To investigate this possibility directly, we made both in vivo and in vitro mixes of thymocytes possessing different alleles of CD8 (Ly-2.1 and Ly-2.2). Under these experimental conditions, we detected Ly-2.2 on the surface of thymocytes that were genetically Ly-2.1+ and incapable of synthesizing Ly-2.2. These data indicate that thymocytes can express cell surface CD8 molecules which they have not produced but have acquired from other cells in their environment. Thus, the present study indicates that low-level surface expression of cell surface CD4/CD8 differentiation molecules does not necessarily identify distinct thymocyte subpopulations.
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