TCR-β chains derived from peripheral γδ T cells can take part in αβ T-cell development

Between 10 and 20% of the peripheral γδ T cells express cytoplasmic TCR-β proteins, but whether such TCR-β chains can partake in αβ T-cell development has never been systematically investigated. Therefore, we reconstituted the T-cell compartment of CD3ε-deficient mice with Pax5-TCR-β deficient proB cells expressing, via a retroviral vector, TCR-β chains from either peripheral γδ or αβ T cells. Recipient thymi reconstituted with proB cells containing empty vector were small (<15 × 10⁶ cells), contained few γδ T but no αβ T cells. In contrast, thymi from mice receiving proB cells containing γδ or αβ T-cell-derived TCR-β chains contained 80-130 × 10⁶ cells, and showed a normal CD4, CD8 and αβ TCR expression pattern. However, regardless of the source of TCR-β chain, reconstituted mice rapidly showed signs of autoimmunity dying 5-15wk following reconstitution. Autoimmune disease induction could be prevented by co-transfer of Treg cells thereby allowing the functionality of the generated T cells to be assessed. Results obtained show that TCR-β chains from γδ T cells can efficiently take part in αβ T-cell development. The implications of these findings for γδ T-cell development will be discussed.