Immature hematopoietic cells display selective requirements for adhesion- and degranulation-promoting adaptor protein in development and homeostatsis
Open Access
- 24 October 2007
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 37 (11), 3208-3219
- https://doi.org/10.1002/eji.200737094
Abstract
Adhesion- and degranulation-promoting adaptor protein (ADAP) modulates T cell development and function and promotes TCR signaling. Regulation of ADAP protein expression during thymopoiesis and in development of other hematopoietic lineages has not been explored. Using intracellular staining, we detected ADAP protein in bone marrow lymphocyte precursors. Like its binding partner SH2-containing leukocyte phosphoprotein of 76 kDa, ADAP is dynamically regulated during thymocyte positive selection. ADAP is also found in unconventional thymocytes, including NKT, CD8αα, and TCRγδ T cells. In peripheral T cells, ADAP is up-regulated after TCR stimulation and with acquisition of memory status. Although absent in splenic B cells, ADAP is present in pro-B cells, as well as in BM erythrocyte and myeloid progenitors. Studies with radiation chimeras show that ADAP is dispensable for NKT, CD8αα and TCRγδ T cell development, while confirming that ADAP is required for optimal development of conventional TCRαβ T cells in the thymus. Interestingly, ADAP is necessary for CD8αα homeostasis in the small intestinal epithelium, yet is dispensable for optimal reconstitution of splenic B cell populations. Our observations highlight the dynamic regulation of ADAP during T cell maturation and document expression patterns that suggest a possible role for ADAP in development of non-T hematopoietic lineages.Keywords
This publication has 50 references indexed in Scilit:
- The ADAP/SKAP55 Signaling Module Regulates T-Cell Receptor-Mediated Integrin Activation through Plasma Membrane Targeting of Rap1Molecular and Cellular Biology, 2006
- Circulating hematopoietic progenitors with T lineage potentialNature Immunology, 2004
- SLP-76 Regulates Fcγ Receptor and Integrin Signaling in NeutrophilsImmunity, 2003
- Positive and Negative Selection of T CellsAnnual Review of Immunology, 2003
- β2 Integrins and ICAM-1 Are Involved in Establishment of the Intestinal Mucosal T Cell CompartmentImmunity, 1996
- The Biology of Hematopoietic Stem CellsAnnual Review of Cell and Developmental Biology, 1995
- T cell receptor antagonist peptides induce positive selectionCell, 1994
- Signal transduction by lymphocyte antigen receptorsCell, 1994
- Control points in early T-cell developmentImmunology Today, 1993
- Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors.The Journal of Experimental Medicine, 1986