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Positive selection of extrathymically developed T cells by self-antigens
H Yamada1, T Ninomiya, A Hashimoto
1Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. hisako@bioreg.kyushu-u.ac.jp
The Journal of Experimental Medicine
|August 26, 1998
Summary
Extrathymically developed T cells are positively selected by self-antigens, not deleted. This study reveals insights into peripheral T cell selection and function outside the thymus.
Area of Science:
- Immunology
- T cell biology
- Peripheral immune system development
Background:
- T cells typically mature in the thymus via positive and negative selection.
- Extrathymic T cell development occurs outside the thymus, but their selection mechanisms remain unclear.
Purpose of the Study:
- To investigate the selection processes governing extrathymically developed T cells.
- To analyze the role of self-antigens in the selection of T cells developing outside the thymus.
Main Methods:
- Reconstitution of thymectomized mice with transgenic bone marrow cells expressing H-Y antigen-specific T cell receptor (TCR).
- Analysis of T cell populations, including surface marker expression (CD3, IL-2Rbeta, NK1.1) and cytokine production (interferon gamma, IL-4) following TCR cross-linking.
Main Results:
- T cells with self-antigen-specific TCR were not deleted in thymectomized male recipients.
- Absence of H-Y antigen-specific T cells in thymectomized females suggests positive selection by self-antigen.
- Extrathymically developed T cells (CD3(int)IL-2Rbeta+NK1.1(-)) produced interferon gamma but not IL-4, mirroring cells in normal mice.
Conclusions:
- Extrathymic T cell development involves positive selection by self-antigens.
- CD3(int)IL-2Rbeta+NK1.1(-) T cells developing extrathymically are likely positively selected by self-antigens.
- Findings shed light on alternative T cell maturation pathways and their functional characteristics.