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ß and 
T Cell Development Using Chimeric Mice with a Low Competitive Hematopoietic Environment1
*
Institut National de la Santé et de la Recherche Médicale U429, Hôpital Necker-Enfants Malades, Paris, France;
Laboratory for Cytokines and Lymphoid Development, Institut Pasteur, Paris, France;
Ludwig Institute for Cancer Research, Eplainger, Switzerland;
§
Babraham Institute, Babraham, Cambridge, United Kingdom; and
¶
National Institute for Medical Research, London, United Kingdom
The Syk protein tyrosine kinase (PTK) is essential for B, but not T
or NK, cell development, although certain T cell subsets (i.e., 
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 T cells was arrested
in Syk-/-
RAG2-/- chimeras. In striking
contrast, when hosts were the newly established alymphoid RAG2 x
common cytokine receptor -chain (RAG2/c)
mice, Syk-/- chimeras
developed intestinal T cells as well as other T cell subsets
(including 
ß T cells, NK1.1+ ß T cells,
and splenic and thymic 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 T cell lineage to
develop.
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  E. H. Palacios and A. Weiss Distinct roles for Syk and ZAP-70 during early thymocyte development J. Exp. Med., July 9, 2007; 204(7): 1703 - 1715. [Abstract] [Full Text] [PDF]
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 A. Mocsai, H. Zhang, Z. Jakus, J. Kitaura, T. Kawakami, and C. A. Lowell G-protein-coupled receptor signaling in Syk-deficient neutrophils and mast cells Blood, May 15, 2003; 101(10): 4155 - 4163. [Abstract] [Full Text] [PDF]
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 T. Jinquan, L. Anting, H. H. Jacobi, C. Glue, C. Jing, L. P. Ryder, H. O. Madsen, A. Svejgaard, P. S. Skov, H.-J. Malling, et al. CXCR3 Expression on CD34+ Hemopoietic Progenitors Induced by Granulocyte-Macrophage Colony-Stimulating Factor: II. Signaling Pathways Involved J. Immunol., October 15, 2001; 167(8): 4405 - 4413. [Abstract] [Full Text] [PDF]
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