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International Immunology, Vol. 11, No. 2, 169-177, February 1999
© 1999 Japanese Society for Immunology

Differential effects of manipulating signaling in early T cell development in intestinal intraepithelial lymphocytes and thymocytes

Stephanie T. Page1,2, Lisa Y. Bogatzki1,2, Jessica A. Hamerman1,2, Marie Malissen4, Roger M. Perlmutter1,2,3,5 and Ann M. Pullen1,2,6

1 Howard Hughes Medical Institute, and
2 Departments of Immunology, and
3 Biochemistry and Medicine (Medical Genetics), University of Washington, Seattle, WA 98195, USA
4 Centre d'Immunolgie, INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseilles Cedex 9, France

Correspondence to: A. M. Pullen, Department of Pathology and Microbiology, School of Medical Sciences, Bristol University, University Walk, Bristol BS8 1TD, UK

A pre-TCR–CD3 signal is required for the efficient maturation of CD4CD8 thymocytes to the CD4+CD8+ stage. This study addressed whether a similar signal is required for maturation of intestinal intraepithelial lymphocytes (IEL) that may develop extrathymically. We have shown previously that IEL from mice deficient for CD3-associated {zeta} chains include an immature population of CD3CD8{alpha}{alpha}+ cells expressing cytoplasmic TCR ß chains but lacking detectable surface TCR{alpha}ß, CD16 and B220. Here we stimulated the appearance of such IEL in {epsilon}+/–{zeta}–/– mice by expression of an activated Lck transgene or in vivo treatment with anti-CD3{epsilon}. Anti-CD3{epsilon} treatment of RAG-deficient animals also yielded CD16B220 IEL. In contrast, expression of a TCRß transgene in rag-1–/– mice did not stimulate the appearance of CD3CD8{alpha}{alpha}+CD16B220 cells. Taken together these data indicate that although anti-CD3{epsilon} treatment and LckF505 assist in catalyzing a CD16+B220+ -> CD16B220 transition, these manipulations are not equivalent to a pre-TCR signal in IEL lymphocytes.

Keywords: CD3{varepsilon}, development, Fyn, intraepithelial lymphocyte, Lck, thymocyte

5 Present address: Merck Research Laboratories, PO Box 2000, RY80-A1, 126 East Lincoln Avenue, Rahway, NJ 07065, USA

6 Present address: Department of Pathology and Microbiology, School of Medical Sciences, Bristol University, University Walk, Bristol BS8 1TD, UK

Transmitting editor: E. Simpson


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