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Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo

Item Type:Article
Title:Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo
Creators Name:Na, I.K. and Markley, J.C. and Tsai, J.J. and Yim, N.L. and Beattie, B.J. and Klose, A.D. and Holland, A.M. and Ghosh, A. and Rao, U.K. and Stephan, M.T. and Serganova, I. and Santos, E.B. and Brentjens, R.J. and Blasberg, R.G. and Sadelain, M. and van den Brink, M.R.M.
Abstract:We have developed a dual bioluminescent reporter system allowing noninvasive, concomitant imaging of T-cell trafficking, expansion, and activation of nuclear factor of activated T cells (NFAT) in vivo. NFAT activation plays an important role in T-cell activation and T-cell development. Therefore we used this system to determine spatial-temporal activation patterns of (1) proliferating T lymphocytes during graft-versus-host disease (GVHD) and (2) T-cell precursors during T-cell development after allogeneic hematopoietic stem cell transplantation (HSCT). In the first days after HSCT, donor T cells migrated to the peripheral lymph nodes and the intestines, whereas the NFAT activation was dominant in the intestines, suggesting an important role for the intestines in the early stages of alloactivation during development of GVHD. After adoptive transfer of in vitro-derived T-cell receptor (TCR) H-Y transgenic T-cell precursors into B6 (H-2(b)) hosts of both sexes, NFAT signaling and development into CD4(+) or CD8(+) single-positive cells could only be detected in the thymus of female recipients indicating either absence of positive selection or prompt depletion of double-positive thymocytes in the male recipients. Because NFAT plays an important role in a wide range of cell types, our system could provide new insights into a variety of biologic processes.
Keywords:3T3 Cells, Adoptive Transfer, Cell Line, Cell Movement, Cell Proliferation, Genetic Promoter Regions, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Jurkat Cells, Lentivirus, Luciferases, Luminescence, Luminescent Measurements, Lymphocyte Activation, NFATC Transcription Factors, T-Lymphocytes, T-Lymphoid Precursor Cells, Tumor Cell Line, Animals, Mice
Publisher:American Society of Hematology
Page Range:e18-e25
Date:16 September 2010
Official Publication:https://doi.org/10.1182/blood-2009-12-259432
PubMed:View item in PubMed

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