| First Author | Colucci F | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 10 | Pages | 5140-5 |
| PubMed ID | 10799872 | Mgi Jnum | J:124430 |
| Mgi Id | MGI:3721502 | Doi | 10.4049/jimmunol.164.10.5140 |
| Citation | Colucci F, et al. (2000) A new look at Syk in alpha beta and gamma delta T cell development using chimeric mice with a low competitive hematopoietic environment. J Immunol 164(10):5140-5 |
| abstractText | 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 cells 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 chimeras generated by using Syk-deficient fetal liver hematopoietic stem cells (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 for Syk in this process. This novel function of Syk in T cell development was mapped to the CD44-CD25+ stage. According to previous reports, development of intestinal gamma delta T cells was arrested in Syk-/- -->RAG2-/- chimeras. In striking contrast, when hosts were the newly established alymphoid 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. These results attest to the utility of chimeric mice generated in a low competitive hematopoietic environment to evaluate more accurately the impact of lethal mutations on lymphoid development. Furthermore, they suggest that Syk intervenes in early T cell development independently of ZAP-70, and demonstrate that Syk is not essential for the intestinal gamma delta T cell lineage to develop. |
