Are the IL-2 receptors expressed in the murine fetal thymus functional?
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 approximately equal to 20 pM) and low (kD approximately equal to 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.
Zůñiga-Pflücker
J C
JC
Biological Response Modifiers Program, National Cancer Institute, Bethesda, Maryland 20892.
Smith
K A
KA
Tentori
L
L
Pardoll
D M
DM
Longo
D L
DL
Kruisbeek
A M
AM
D000818:Animals; D005260:Female; D005333:Fetus / Q000276:immunology*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2