Are the IL-2 Receptors Expressed in the Murine Fetal Thymus Functional?

Juan Carlos Zoúñiga-Pflücker,Lucio Tentori,Dan L Longo,Drew M Pardoll,Kendall A Smith,Ada M Kruisbeek

doi:10.1155/1990/59576

Abstract

It is well established that the majority of murine fetal thymocytes (day 15 of gestation) express receptors for interleukin 2 (IL-2), but the functional significance of these IL-2 receptors (IL-2Rs) is not clear. In situ hybridization data show a developmentally regulated expression of IL-2 and IL-2R mRNA. IL-2 binding studies were performed on fetal thymocytes and the results show the presence of both high (kD ≅ 20 pM) and low (kD ≅ 10 nM) affinity IL-2Rs. These IL-2Rs are indeed functional: intact fetal thymic lobes (but not cell suspensions) cultured in IL-2 exhibited an in vitro proliferative response at 20 pM of IL-2, corresponding with the presence of a functional high-affinity IL-2R on fetal thymocytes. The IL-2-dependent growth was primarily observed in the IL-2R + thymic subset, which contains the CD3-/CD4-/CD8- precursor thymocytes. Furthermore, in vitro blocking of IL-2 in intact fetal thymic lobes resulted in a reduction in the cell yield, which predominantly affected the expansion of the immature CD3-/CD4-/CD8-thymocytes. Our findings strongly support the concept that the IL-2/IL-2R pathway is responsible for the proliferation of precursor cells within the fetal thymus.

Highlights

It is accepted that interleukin 2 (IL-2) is responsible for promoting the growth of mature T cells subsequent to their activation by antigen (Smith, 1984)
Our results indicate that IL-2 and IL-2 receptors (IL-2Rs) mRNA undergo developmentally regulated expression, and that the IL-2Rs expressed in fetal thymocytes are functional high-affinity receptors
Using a quantitative method of in situ hybridization, we demonstrated that IL-2 and IL-2R mRNA are expressed simultaneously in a small fraction of developing murine fetal thymocytes as early as day 13 of gestation (Fig. 1)

Summary

Introduction

It is accepted that interleukin 2 (IL-2) is responsible for promoting the growth of mature T cells subsequent to their activation by antigen (Smith, 1984). The first and most crucial question regarding the possible role of the .IL-2/ILo2R pathway in T-cell development is whether the IL-2R expressed on fetal thymocytes is functional.

Results

Conclusion