CD135 (Flk2/Flt3) Expression by Human Thymocytes Delineates a Possible Role of FLT3-Ligand in T-Cell Precursor Proliferation and Differentiation

BERTHO, J.-M.
CHAPEL, A.
LOILLEUX, S.
FRICK, J.
AIGUEPERSE, J.
GORIN, N. C.
GOURMELON, P.

*Section Autonome de Radiobiologie Appliquée à la Médecine, Institut de Protection et de Sûreté Nucléaire, Fontenay aux Roses, †Laboratoire de thérapie cellulaire et de radioprotection acidentelle, UPRES 1638, Centre Claude Bernard, Paris, and ‡Départment de Protection de la santé de l'Homme et de Dosimétrie, Institut de Protection et de Sûreté Nucléaire, Fontenay aux Roses, France

(Received 2 February 2000; Accepted in revised form 10 March 2000)

Jean-Marc Bertho, Institut de Protection et de Sûreté Nucléaire, Département de Protection de la santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, IPSN, BP n°6, F-92265 Fontenay aux Roses Cédex, France

Scandinavian Journal of Immunology 52(1):p 53-61, July 2000.

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^highCD3⁻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⁺TcRγδ⁺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.