Flt3 ligand expands lymphoid progenitors prior to recovery of thymopoiesis and accelerates T cell reconstitution after bone marrow transplantation

J Immunol. 2007 Mar 15;178(6):3551-7. doi: 10.4049/jimmunol.178.6.3551.

Abstract

Deficient thymopoiesis and retarded recovery of newly developed CD4(+) T cells is one of the most important determinants of impaired immunocompetence after hemopoietic stem cell transplantation. Here we evaluated whether Fms-like tyrosine kinase 3 (Flt3) ligand (FL) alone or combined with IL-7 affects T cell recovery, thymopoiesis, and lymphoid progenitor expansion following bone marrow transplantation in immunodeficient mice. FL strongly accelerated and enhanced the recovery of peripheral T cells after transplantation of a low number of bone marrow cells. An additive effect on T cell recovery was not observed after coadministration of IL-7. Lineage(-)sca-1(+)c-kit(+)flt3(+) lymphoid progenitor cell numbers were significantly increased in bone marrow of FL-treated mice before recovery of thymopoiesis. Thymocyte differentiation was advanced to more mature stages after FL treatment. Improved T cell recovery resulted in better immunocompetence against a post-bone marrow transplantation murine CMV infection. Collectively, our data suggest that FL promotes T cell recovery by enhanced thymopoiesis and by expansion of lymphoid progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Bone Marrow Transplantation*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Interleukin-7 / pharmacology
  • Lymphopoiesis / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Recovery of Function / drug effects
  • Recovery of Function / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • IL7 protein, human
  • Interleukin-7
  • Membrane Proteins
  • flt3 ligand protein