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The role of PSGL-1 in T cell migration and homeostasis

University of British Columbia

P-Selectin Glycoprotein Ligand-1 (PSGL-1) is an extracellular glycoprotein expressed on most leukocytes that is important for rolling and tethering of activated leukocytes to areas of inflammation through direct interactions with P-selectin, E-selectin and L-selectin. However, PSGL-1null mice showed subtle defects in their homeostatic T cell profile that cannot be adequately explained by a defect in migration of activated leukocytes. PSGL-1null mice had a reduced number of CD4+ and CD8+ T cells in the peripheral blood but not in the lymph nodes and spleen. T cell subset analysis revealed that there was a severe reduction of naïve T cells in the peripheral blood and a moderate reduction of naïve T cells in the lymph nodes whereas other T cell compartments were not as affected. Here we determined that PSGL-1 was important for the homing of T cells to secondary lymphoid organs and that PSGL-1 functioned independently of selectin interaction. PSGL-1 enhanced T cell homing through an interaction with secondary lymphoid chemokines CCL21 and CCL19. We have also shown that PSGL-1null T cells are delayed in leaving the lymph nodes suggesting PSGL-1 is important in the movement of T cells both in and out of lymph nodes. Therefore, the reduced ability of PSGL-1null T cells to enter lymph nodes and receive survival factors may contribute to disturbed T cell subsets in peripheral blood and lymph nodes of PSGL-1null mice. There is evidence of spontaneous CD8+ T cell specific proliferation in PSGL-1null cells in lymphoreplete environments. This appears to be caused by a combination of factors, namely an increase in lymph node residence time as well as a more rapid proliferative response to the homeostatic cytokines IL-15, IL-2 and IL-4. However, PSGL-1null T cells are also less viable both in vivo and in vitro. Therefore, spontaneous proliferation may be a compensatory mechanism that balances T cell levels to normal in lymph nodes and spleens of PSGL-1null mice. These findings collectively demonstrate a novel, selectin-independent role for PSGL-1 on T cells under non-inflammatory conditions both in T cell homing to secondary lymphoid organs as well as maintenance of T cell homeostasis.

Text

2012-02-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/36927

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/