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Updated: Jun 24, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells
Y Takahama1, E W Shores, A Singer
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.
Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.
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