Correction of T cell deficiency in ZAP-70 knockout mice by simple intraperitoneal adoptive transfer of thymocytes

Summary

The tyrosine kinase ZAP-70 (zeta-chain associated protein of 70 kDa) plays a key role in T cell development and signaling. In the absence of ZAP-70, T cell development is arrested in the CD4⁺CD8⁺ double positive stage, thus ZAP-70 homozygous knockout (ZAP-70^-/-) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency.

We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70^-/- mice. We used a single intraperitoneal (ip.) injection to deliver donor thymocytes to the recipients.

Here, we show that after ip. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where most probably donor-originated CD4^-CD8^- double negative thymocytes restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70^-/- mice as late as 8 months after ip. injection.

We demonstrate that a simple, ip. injection of ZAP-70^+/+ thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70 deficient mice. This article is protected by copyright. All rights reserved.