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FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs.

Hofmann, Matthias and Brinkmann, Volker and Zerwes, Hans-Guenter (2006) FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs. International Immunopharmacology, 6 (13-14). pp. 1902-1910. ISSN 1567-5769

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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: T lymphocyte; FTY720; Cell trafficking; Cell surface molecules; Flow cytometry
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Date Deposited: 14 Dec 2009 13:58
Last Modified: 31 Jan 2013 01:13
URI: https://oak.novartis.com/id/eprint/556

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