FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs

Int Immunopharmacol. 2006 Dec 20;6(13-14):1902-10. doi: 10.1016/j.intimp.2006.07.030. Epub 2006 Aug 30.

Abstract

The sphingosine-1-phosphate receptor agonist FTY720 induces lymphopenia by inhibiting lymphocyte egress from thymus and lymph nodes. The immediate effect of the drug on T cells in blood and lymphoid tissues is well documented, however effects on peripheral T cell sub-populations have not been studied. We therefore analyzed the changes in T cell subset compositions in liver, lung, kidney, spleen, lymph nodes and blood induced by FTY720-treatment using 9-parameter flow cytometry. In untreated mice, naive T cells were present in all peripheral organs. Naive T cells were depleted from peripheral organs within 3 days by FTY720, and with slower kinetics from lymphoid organs. Antigen-experienced T cell subsets were less affected by FTY720-treatment and substantial numbers were retained in the periphery. The proportion of CD8(+)CD44(+)CD43(+) Gr-1(+) effector memory cells increased after FTY720-treatment, while that of CD8(+)CD44(+)CD62L(+) central memory cells was unchanged. Our data demonstrate that naive T cells pass peripheral tissues as part of their default recirculation pathway. FTY720 treatment primarily affects the recirculation of naive and central memory cells, both of which re-circulate through lymph nodes on a regular basis, but does not influence effector memory cells. This suggests that treatment with FTY720 may not interfere with immune functions mediated locally by tissue-resident peripheral effector/memory T cells.

MeSH terms

  • Animals
  • Antigens, CD / analysis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Count
  • Cell Movement / drug effects
  • Female
  • Fingolimod Hydrochloride
  • Flow Cytometry
  • Immunosuppressive Agents / pharmacology
  • Kidney / cytology
  • Kidney / drug effects
  • Liver / cytology
  • Liver / drug effects
  • Lung / cytology
  • Lung / drug effects
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymphocyte Depletion*
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Propylene Glycols / pharmacology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Spleen / cytology
  • Spleen / drug effects
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD
  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine