Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution

Terry J. Fry, Manoj Sinha, Matthew Milliron, Yu Waye Chu, Veena Kapoor, Ronald E. Gress, Elaine Thomas, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Despite recent progress in our understanding of the biology of T-cell homeostasis, clinically available therapies to substantially improve immune reconstitution in patients sustaining T-cell depletion are lacking. T cells are regenerated via a dynamic interplay between thymopoiesis and thymic-independent homeostatic peripheral expansion (HPE). Using athymic mice subjected to T-cell depletion, we observed that HPE is critically dependent on dendritic cells (DCs) for presentation of antigen, raising the possibility that the availability of DCs might be limiting in vivo for HPE to occur efficiently. Indeed, flt3 ligand (flt3L) treatment of athymic mice subjected to T-cell depletion (without DC depletion) substantially enhanced HPE and improved immune competence. Following bone marrow transplantation (BMT) in athymic hosts, both dendritic cells and T cells were profoundly depleted and flt3L therapy restored DC numbers and enhanced HPE. In addition, thymus-bearing BMT recipients treated with flt3L regenerated increased numbers of thymic-dependent progeny with increased numbers of T-cell receptor excision circle (TREC)-positive T cells, indicating increased thymopoiesis. Therefore, flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration.

Original languageEnglish (US)
Pages (from-to)2794-2800
Number of pages7
JournalBlood
Volume104
Issue number9
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

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T-cells
T-Lymphocytes
Dendritic Cells
Bone Marrow Transplantation
Nude Mice
Bone
Bearings (structural)
Thymus
flt3 ligand protein
Antigen Presentation
T-Cell Antigen Receptor
Mental Competency
Thymus Gland
Regeneration
Homeostasis
Therapeutics
Cell Count
Availability
Antigens

ASJC Scopus subject areas

  • Hematology

Cite this

Fry, T. J., Sinha, M., Milliron, M., Chu, Y. W., Kapoor, V., Gress, R. E., ... Mackall, C. L. (2004). Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution. Blood, 104(9), 2794-2800. https://doi.org/10.1182/blood-2003-11-3789

Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution. / Fry, Terry J.; Sinha, Manoj; Milliron, Matthew; Chu, Yu Waye; Kapoor, Veena; Gress, Ronald E.; Thomas, Elaine; Mackall, Crystal L.

In: Blood, Vol. 104, No. 9, 01.11.2004, p. 2794-2800.

Research output: Contribution to journalArticle

Fry, TJ, Sinha, M, Milliron, M, Chu, YW, Kapoor, V, Gress, RE, Thomas, E & Mackall, CL 2004, 'Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution', Blood, vol. 104, no. 9, pp. 2794-2800. https://doi.org/10.1182/blood-2003-11-3789
Fry TJ, Sinha M, Milliron M, Chu YW, Kapoor V, Gress RE et al. Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution. Blood. 2004 Nov 1;104(9):2794-2800. https://doi.org/10.1182/blood-2003-11-3789
Fry, Terry J. ; Sinha, Manoj ; Milliron, Matthew ; Chu, Yu Waye ; Kapoor, Veena ; Gress, Ronald E. ; Thomas, Elaine ; Mackall, Crystal L. / Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution. In: Blood. 2004 ; Vol. 104, No. 9. pp. 2794-2800.
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