Details

Autor(en) / Beteiligte

• Kadlecek, Theresa A
• van Oers, Nicolai S. C
• Lefrancois, Leo
• Olson, Sara
• Finlay, Deborah
• Chu, David H
• Connolly, Kari
• Killeen, Nigel
• Weiss, Arthur

Titel

Differential Requirements for ZAP-70 in TCR Signaling and T Cell Development

Ist Teil von

• The Journal of immunology (1950), 1998-11, Vol.161 (9), p.4688-4694

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

1998

Quelle

MEDLINE

Beschreibungen/Notizen

• The Syk/ZAP-70 family of protein tyrosine kinases is indispensable for normal lymphoid development. Syk is necessary for the development of B cells and epithelial gammadelta T cells, whereas ZAP-70 is essential for the normal development of T cells and TCR signaling. In this study, we show that although development of the alphabeta lineage was arrested in the thymus, CD3-positive T cells, primarily of the gammadelta lineage, were present in the lymph nodes of mice lacking ZAP-70. Moreover, in the absence of ZAP-70, dendritic epidermal T cells were fewer in number and of abnormal morphology, and intestinal intraepithelial lymphocytes, normally containing a large proportion of gammadelta T cells, were markedly reduced. These data suggest that gammadelta T cells show a variable dependence upon ZAP-70 for their development. Biochemical analyses of thymocytes revealed a lack of basal zeta-chain tyrosine phosphorylation. However, several other substrates were inducibly tyrosine phosphorylated following TCR stimulation. Thus, TCR-mediated signaling in ZAP-70-deficient thymocytes is only partially impaired. These studies suggest that Syk compensates only partially for the loss of ZAP-70, and that there is an absolute requirement of ZAP-70 for alphabeta T cells and epithelial gammadelta T cells, but not for some gammadelta T cells in peripheral lymphoid tissues.