Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells.

TLDR

The study evaluates the in vivo differentiation capacity of dLy‑1 thymocytes within the thymus. The authors used multiparameter flow cytometry and radiation chimeric mice with Ly‑1 or Ly‑5 congenic markers to demonstrate that transferred dLy‑1 cells sequentially produce cortical and medullary thymocytes. A small (<5%) dLy‑1 thymocyte subset can sequentially generate cortical and medullary thymocytes in vivo, with donor‑derived output proportional to transferred cells, limited self‑renewal, and transient repopulation, indicating that dLy‑1 cells are very early intrathymic precursors.

Abstract

A minor subpopulation of adult murine thymocytes (less than 5%) that is Lyt-2-, L3T4-, and expresses low levels of Ly-1 (designated dLy-1 [dull] thymocytes) has been identified, isolated, and characterized. This study assesses the differentiation potential of dLy-1 thymocytes in the thymus in vivo. Using multiparameter flow cytometry, radiation chimeras of C57BL/6 mice congenic at the Ly-1 or Ly-5 locus, and allelic markers to discriminate host and donor, we showed that transferred dLy-1 cells were able to generate thymocytes expressing both cortical and medullary phenotypes in a sequential manner. The proportion of donor-derived thymocytes obtained was directly related to the number of dLy-1 thymocytes transferred. Transfer of purified Lyt-2+ or Lyt-2+ + L3T4+ thymocytes, which constitute greater than 94% of total thymocytes, failed to generate any donor-derived thymocytes in irradiated recipients. Transfer of bone marrow (BM) cells produced the same sequential pattern of differentiation as that produced by dLy-1 cells, but was delayed by 4-5 d. Transferred dLy-1 thymocytes exhibited a limited capacity for self-renewal, and resulted in a single wave of differentiation in irradiated hosts. Thus, thymic repopulation by donor-derived cells after transfer of dLy-1 thymocytes was transient, while repopulation by BM was permanent. These findings suggest that the isolated dLy-1 thymocytes described herein are precursor thymocytes that represent a very early stage in intrathymic development.