Flt3 ligand augmentation of T cell mitogenesis and expansion of type 1 effector/memory T cells.
Herein we report mechanisms whereby Flt3 ligand (FL) augments steady state T cell activity in addition to the expansion of dendritic cells (DCs). We demonstrate that in vivo administration of FL increases the frequency and absolute number of effector/memory T cells and preferentially expands T cells that express a type-1 cytokine phenotype. In addition, FL enhances T cell proliferative responses to Concanavalin A that directly correlated with increased frequencies in effector/memory T cells and expansion of lymphoid-derived (type 1) DCs (DC1s). Together, these data demonstrate that mechanisms of FL-induced T cell regulation include not only the expansion of DC subsets, but also the preferential expansion of type 1 -effector/memory T cell populations, and suggest multiple mechanisms of action for FL as a vaccine adjuvant and as a therapeutic modality.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-7660, USA. rlmosley@unmc.edu
R Lee
RL
Mosley
Prahlad
P
Parajuli
Vladimir
V
Pisarev
Jennifer
J
Chavez
Amy
A
Meeks
Amy
A
Steffel
Cheryl
C
Leutzinger
James E
JE
Talmadge
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology* / Q000502:physiology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D008565:Membrane Proteins; C084881:flt3 ligand protein