دورية أكاديمية
DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice
| العنوان: | DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice |
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| المؤلفون: | Randall, Katrina, Chan, Stephanie, Ma, Cindy, Fung, Ivan, Mei, Angela (Yan), Yabas, Mehmet, Tan, Andy, Arkwright, Peter D, Al Suwairi, Wafaa, Reyes, Saul Oswaldo Lugo, Yamazaki-Nakashimada, Marco A., Garcia-Cruz, Maria de la Luz, Smart, Joanne M., Picard, Capucine, Okada, Satoshi, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Lambe, Teresa, Cornall, Richard J, Russell, Sarah, Oliaro, Jane, Tangye, Stuart, Bertram, Edward, Goodnow, Christopher |
| المصدر: | Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press |
| المجموعة: | Australian National University: ANU Digital Collections |
| مصطلحات موضوعية: | Keywords: CD45RA antigen, chemokine receptor CCR7, lymphocyte function associated antigen 1, protein, protein dock8, unclassified drug, animal cell, animal experiment, animal model, animal tissue, article, CD8+ T lymphocyte, cell division, cell function, cell polar |
| الوصف: | In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA+CCR7? phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0022-1007 |
| العلاقة: | http://hdl.handle.net/1885/39046Test; https://openresearch-repository.anu.edu.au/bitstream/1885/39046/5/DOCK_8_deficiency_K_Randall_J_Exp_Med.pdf.jpgTest; https://openresearch-repository.anu.edu.au/bitstream/1885/39046/7/01_Randall_DOCK8_deficiency_impairs_CD8_T_2011.pdf.jpgTest |
| DOI: | 10.1084/jem.20110345 |
| الإتاحة: | https://doi.org/10.1084/jem.20110345Test http://hdl.handle.net/1885/39046Test https://openresearch-repository.anu.edu.au/bitstream/1885/39046/5/DOCK_8_deficiency_K_Randall_J_Exp_Med.pdf.jpgTest https://openresearch-repository.anu.edu.au/bitstream/1885/39046/7/01_Randall_DOCK8_deficiency_impairs_CD8_T_2011.pdf.jpgTest |
| حقوق: | Author/s retain copyright |
| رقم الانضمام: | edsbas.F8E2E9D0 |
| قاعدة البيانات: | BASE |
| تدمد: | 00221007 |
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| DOI: | 10.1084/jem.20110345 |