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Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment.

Publication ,  Journal Article
Haynes, BF; Heinly, CS
Published in: J Exp Med
April 1, 1995

To determine events that transpire during the earliest stages of human T cell development, we have studied fetal tissues before (7 wk), during (8.2 wk), and after (9.5 wk to birth) colonization of the fetal thymic rudiment with hematopoietic stem cells. Calculation of the approximate volumes of the 7- and 8.2-wk thymuses revealed a 35-fold increase in thymic volumes during this time, with 7-wk thymus height of 160 microM and volume of 0.008 mm3, and 8.2-wk thymus height of 1044 microM and volume of 0.296 mm3. Human thymocytes in the 8.2-wk thymus were CD4+ CD8 alpha+ and cytoplasmic CD3 epsilon+ cCD3 delta+ CD8 beta- and CD3 zetta-. Only 5% of 8-wk thymocytes were T cell receptor (TCR)-beta+, < 0.1% were TCR-gamma+, and none reacted with monoclonal antibodies against TCR-delta. During the first 16 wk of gestation, we observed developmentally regulated expression of CD2 and CD8 beta (appearing at 9.5 wk), CD1a,b, and c molecules (CD1b, then CD1c, then CD1a), TCR molecules (TCR-beta, then TCR-delta), CD45RA and CD45RO isoforms, CD28 (10 wk), CD3 zeta (12-13 wk), and CD6 (12,75 wk). Whereas CD2 was not expressed at the time of initiation of thymic lymphopoiesis, a second CD58 ligand, CD48, was expressed at 8.2 wk, suggesting a role for CD48 early in thymic development. Taken together, these data define sequential phenotypic and morphologic changes that occur in human thymus coincident with thymus colonization by hematopoietic stem cells and provide insight into the molecules that are involved in the earliest stages of human T cell development.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 1, 1995

Volume

181

Issue

4

Start / End Page

1445 / 1458

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocyte Subsets
  • Receptors, Antigen, T-Cell
  • Microscopy, Fluorescence
  • Immunophenotyping
  • Immunology
  • Image Processing, Computer-Assisted
  • Humans
  • Hematopoietic Stem Cells
  • Gestational Age
 

Citation

APA
Chicago
ICMJE
MLA
NLM

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 1, 1995

Volume

181

Issue

4

Start / End Page

1445 / 1458

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocyte Subsets
  • Receptors, Antigen, T-Cell
  • Microscopy, Fluorescence
  • Immunophenotyping
  • Immunology
  • Image Processing, Computer-Assisted
  • Humans
  • Hematopoietic Stem Cells
  • Gestational Age