Identification of an early T cell progenitor for a pathway of T cell maturation in the bone marrow

Identification of an early T cell progenitor for a pathway of T cell maturation in the bone marrow

Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5111

Edited by Irving L. Weissman, Stanford University School of Medicine, Stanford, CA, and approved October 12, 1999 (received for review August 10, 1999)

Abstract

We have identified a rare (≈0.05–0.1%) population of cells (Thy-1^hiCD16⁺CD44^hiCD2⁻TCRαβ⁻B220⁻Mac-1⁻NK1.1⁻) in the adult mouse bone marrow that generates CD4⁺ and CD8⁺ TCRαβ⁺ T cells after tissue culture for 48 hr in the presence of Ly5 congenic marrow cells. The essential stages in the maturation of the progenitors were determined; the stages included an early transition from CD2⁻CD16⁺CD44^hiTCRαβ⁻ to CD2⁺CD16^int/−CD44^int/−TCRαβ⁻ cells, and a later transition to CD4⁺CD8⁺TCRαβ⁺ double-positive T cells that rapidly generate the CD4⁺ and CD8⁺ single-positive T cells. The maturation of the progenitors is almost completely arrested at the CD2⁺TCRαβ⁻ stage by the presence of mature T cells at the initiation of cultures. This alternate pathway is supported by the marrow microenvironment; it recapitulates critical intermediary steps in intrathymic T cell maturation.

Footnotes

↵ * To whom reprint requests should be addressed at: Stanford University School of Medicine, 300 Pasteur Drive, Room S105B, Stanford, CA 94305. E-mail: sstrober{at}stanford.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

PE,

phycoerythrin;

TCR,

T cell receptor