CD135 (Flk2/Flt3) expression by human thymocytes delineates a possible role of FLT3-ligand in T-cell precursor proliferation and differentiation.
The expression of the Flk2/Flt3 molecule (CD135), the receptor for Flt3 ligand (FL), was investigated in the human thymus. Results showed that there is a high level of expression of CD135 by thymocyte populations, especially by intrathymic T-cell precursor populations. As these results suggested a role for FL in the regulation of thymic T-cell precursor differentiation and/or proliferation, we used an in vitro model of thymic stromal cell cultures in order to delineate the activity of FL on human CD7(high)CD3-CD4-CD8- triple negative intrathymic T-cell precursors. Results showed that FL, either alone or in combination with stem cell factor (SCF) induced the proliferation of CD7(high) precursors, but to a lower extent than interleukin-7 (IL-7) or IL-7 + SCF, used as positive controls. In the presence of FL + SCF, CD7(high) cells developed mainly towards a CD11b+ phenotype whereas IL-7 + SCF preferentially induce a CD3+TcRgammadelta+CD8+ phenotype. Taken together, these data suggest that FL may play a role in inducing the proliferation of CD7(high) human intrathymic T-cell precursors, but also in the induction of a myeloid differentiation pathway within the human thymus.
Bertho
J M
JM
Section Autonome de Radiobiologie Appliquée à la Médecine, Institut de Protection et de Sûreté Nucléaire, Fontenay aux Roses, France.
Chapel
A
A
Loilleux
S
S
Frick
J
J
Aigueperse
J
J
Gorin
N C
NC
Gourmelon
P
P
D002454:Cell Differentiation; D002648:Child; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3
D015851:Interleukin-7; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3