PMID- 19962328
OWN - NLM
STAT- MEDLINE
DCOM- 20100209
LR  - 20211020
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 31
IP  - 6
DP  - 2009 Dec 18
TI  - Differential contribution of chemotaxis and substrate restriction to segregation 
      of immature and mature thymocytes.
PG  - 986-98
LID - 10.1016/j.immuni.2009.09.020 [doi]
AB  - T cell development requires sequential localization of thymocyte subsets to 
      distinct thymic microenvironments. To address mechanisms governing this 
      segregation, we used two-photon microscopy to visualize migration of purified 
      thymocyte subsets in defined microenvironments within thymic slices. 
      Double-negative (CD4(-)8(-)) and double-positive (CD4(+)8(+)) thymocytes were 
      confined to cortex where they moved slowly without directional bias. DP cells 
      accumulated and migrated more rapidly in a specialized inner-cortical 
      microenvironment, but were unable to migrate on medullary substrates. In 
      contrast, CD4 single positive (SP) thymocytes migrated directionally toward the 
      medulla, where they accumulated and moved very rapidly. Our results revealed a 
      requisite two-step process governing CD4 SP cell medullary localization: the 
      chemokine receptor CCR7 mediated chemotaxis of CD4 SP cells towards medulla, 
      whereas a distinct pertussis-toxin sensitive pathway was required for medullary 
      entry. These findings suggest that developmentally regulated responses to both 
      chemotactic signals and specific migratory substrates guide thymocytes to 
      specific locations in the thymus.
CI  - Copyright 2009 Elsevier Inc. All rights reserved.
FAU - Ehrlich, Lauren I Richie
AU  - Ehrlich LI
AD  - Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 
      Stanford, CA 94305, USA.
FAU - Oh, David Y
AU  - Oh DY
FAU - Weissman, Irving L
AU  - Weissman IL
FAU - Lewis, Richard S
AU  - Lewis RS
LA  - eng
GR  - R01 CA086065/CA/NCI NIH HHS/United States
GR  - R01 GM045374/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091203
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Receptors, CCR7)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
CIN - Immunity. 2009 Dec 18;31(6):856-8. PMID: 20064445
MH  - Animals
MH  - Chemotaxis/*immunology
MH  - Immunomagnetic Separation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pertussis Toxin/immunology
MH  - Receptors, CCR7/genetics/metabolism
MH  - T-Lymphocyte Subsets/drug effects/*immunology
MH  - Thymus Gland/*immunology
PMC - PMC4106268
MID - NIHMS606287
EDAT- 2009/12/08 06:00
MHDA- 2010/02/10 06:00
PMCR- 2014/07/22
CRDT- 2009/12/08 06:00
PHST- 2009/05/18 00:00 [received]
PHST- 2009/08/30 00:00 [revised]
PHST- 2009/09/21 00:00 [accepted]
PHST- 2009/12/08 06:00 [entrez]
PHST- 2009/12/08 06:00 [pubmed]
PHST- 2010/02/10 06:00 [medline]
PHST- 2014/07/22 00:00 [pmc-release]
AID - S1074-7613(09)00497-X [pii]
AID - 10.1016/j.immuni.2009.09.020 [doi]
PST - ppublish
SO  - Immunity. 2009 Dec 18;31(6):986-98. doi: 10.1016/j.immuni.2009.09.020. Epub 2009 
      Dec 3.