A new look at Syk in alpha beta and gamma delta T cell development using chimeric mice with a low competitive hematopoietic environment

The Syk protein tyrosine kinase (PTK) is essential for B, but not T or NK, cell development, although certain T cell subsets (i.e., gamma delta T cell s of intestine and skin) appear to be dependent on Syk, In this report, we have re-evaluated the role of Syk in T cell development in hematopoietic ch imeras generated by using Syk-deficient fetal liver hematopoietic stem cell s (FL-HSC), We found that Syk(-/-) FL-HSC were vastly inferior to wild-type FL-HSC in reconstituting T cell development in recombinant-activating gene 2 (RAG2)-deficient mice, identifying an unexpected and nonredundant role f or Syk in this process. This novel function of Syk in T cell development wa s mapped to the CD44(-)CD25(+) stage. According to previous reports, develo pment of intestinal gamma delta T cells was arrested in Syk(-/- -)-->RAG2(- /-) chimeras, In striking contrast, when hosts were the newly established a lymphoid RAG2 x common cytokine receptor gamma-chain (RAG2/gamma(c)) mice, Syk(-/-) chimeras developed intestinal gamma delta T cells as well as other T cell subsets (including alpha beta T cells, NK1.1(+) alpha beta T cells, and splenic and thymic gamma delta T cells). However, all Syk-deficient T cell subsets were reduced in number, reaching about 25-50% of controls. The se results attest to the utility of chimeric mice generated in a low compet itive hematopoietic environment to evaluate more accurately the impact of l ethal mutations on lymphoid development. Furthermore, they suggest that Syk intervenes in early T cell development independently of ZAP-70, and demons trate that Syk is not essential for the intestinal gamma delta T cell linea ge to develop.