Lineage Diversion of T Cell Receptor Transgenic Thymocytes Revealed by Lineage Fate Mapping

Abstract

Background: The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of \(TCR\alpha\beta\) lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged \(TCR\alpha\beta\) prematurely at the double negative stage and abnormal TCRαβ populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. Methodology and Principal Findings: To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic \(TCR\alpha\beta\) diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the RORγt-positive \(CD4^{+}8^{+}\) (double positive, DP) stage to accumulate either as \(CD4^{-}8^{-}\) (double negative, DN) or as \(CD8\alpha^{+}\) T cells in lymph nodes or gut epithelium. Likewise, DN \(TCR\alpha\beta\) cells in lymphoid tissue of female mice were not derived from DP thymocytes. Conclusion: The results further support the hypothesis that the premature expression of the \(TCR\alpha\beta\) can divert DN thymocytes into gamma delta lineage cells.