Document Detail


Cell generation within human thymic subsets defined by selective expression of CD45 (T200) isoforms.
MedLine Citation:
PMID:  2138598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the thymus is the source of all mature peripheral T lymphocytes, the majority of thymocytes die intrathymically. Until recently, there has been no phenotypic marker to allow definition of the generative thymocyte lineage, thereby distinguishing those thymocytes committed to death from those which will eventually give rise to thymic emigrants. We believe that expression of the high-molecular-mass isoforms (p190, p205, and/or p220) of the leukocyte common antigen (CD45) distinguishes the thymic generative lineage from the vast majority of thymocytes expressing the low-molecular-mass isoform (p180) of CD45 and committed to die within the thymus. The thymocytes defined by their lack of CD45 p180, the low-molecular-mass isoform, comprise all thymocytes with clonogenic potential and include all major subsets defined by CD4 and CD8. We have proposed that a CD45 p180- lineage exists in the human thymus and that this lineage results in the production of mature thymocytes and thymic emigrants. The objective of the present study was to determine by DNA analysis whether the degree of cell cycling in subsets of human thymus, defined by selective expression of high-molecular-mass isoforms of CD45, was sufficient to account for the generation of thymic emigrants. Multicolor immunofluorescence analysis of surface markers and 7-amino actinomycin D as well as propidium iodide staining was used to measure the DNA content of thymic subsets. Negative depletion methods were used to isolate and characterize human thymocyte subsets defined by CD45 isoform, CD3, CD4, and CD8, and subsequently to determine the cell cycle status of the isolated subsets by flow-cytometric analysis of cellular DNA content. CD3-/lo thymocytes had a high number and CD1-/lo thymocytes a low number of cycling cells, consistent with murine data. CD45 p180- cells, as well as the CD4-(8-) and CD3-(4-)(8-) subsets, which express high molecular-weight CD45 isoforms, exhibited a significant number of cycling cells. Since CD45 p180- thymocytes exhibited a significant number of cycling cells, based on numerical arguments we conclude that this cycling thymocyte fraction is capable of generating the daily requirement of mature thymocytes and thymic emigrants.
Authors:
M Egerton; E Pruski; L M Pilarski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human immunology     Volume:  27     ISSN:  0198-8859     ISO Abbreviation:  Hum. Immunol.     Publication Date:  1990 Apr 
Date Detail:
Created Date:  1990-05-02     Completed Date:  1990-05-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8010936     Medline TA:  Hum Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  333-47     Citation Subset:  IM    
Affiliation:
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Antigens, CD / analysis*
Antigens, CD4 / analysis
Antigens, CD45
Antigens, CD8
Antigens, Differentiation / analysis*
Antigens, Differentiation, T-Lymphocyte / analysis
Cell Cycle
Child
Child, Preschool
DNA / analysis
Flow Cytometry
Histocompatibility Antigens / analysis*
Humans
Infant
Infant, Newborn
Molecular Weight
T-Lymphocytes / immunology
Thymus Gland / cytology,  immunology*
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD4; 0/Antigens, CD8; 0/Antigens, Differentiation; 0/Antigens, Differentiation, T-Lymphocyte; 0/Histocompatibility Antigens; 9007-49-2/DNA; EC 3.1.3.48/Antigens, CD45

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