title: PSGL-1 regulates the migration and proliferation of CD8(+) T cells under homeostatic conditions.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1), a heavily glycosylated sialomucin expressed on most leukocytes, has dual function as a selectin ligand for leukocyte rolling on vascular selectins expressed in inflammation and as a facilitator of resting T cell homing into lymphoid organs. In this article, we document disturbances in T cell homeostasis present in PSGL-1(null) mice. Naive CD4(+) and CD8(+) T cell frequencies were profoundly reduced in blood, whereas T cell numbers in lymph nodes and spleen were at or near normal levels. Although PSGL-1(null) T cells were less efficient at entering lymph nodes, they also remained in lymph nodes longer than PSGL-1(+/+) T cells, suggesting that PSGL-1 supports T cell egress. In addition, PSGL-1(null) CD8(+) T cell proliferation was observed under steady-state conditions and PSGL-1(null) CD8(+) T cells were found to be hyperresponsive to homeostatic cytokines IL-2, IL-4, and IL-15. Despite these disturbances in T cell homeostasis, PSGL-1(null) mice exhibited a normal acute response (day 8) to lymphocytic choriomeningitis virus infection but generated an increased frequency of memory T cells (day 40). Our observations demonstrate a novel pleiotropic influence of PSGL-1 deficiency on several aspects of T cell homeostasis that would not have been anticipated based on the mild phenotype of PSGL-1(null) mice. These potentially offsetting effects presumably account for the near-normal cellularity seen in lymph nodes of PSGL-1(null) mice.
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Krystle M
authors.initials: KM
authors.lastname: Veerman
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Carlow
authors.forename: Iryna
authors.initials: I
authors.lastname: Shanina
authors.forename: John J
authors.initials: JJ
authors.lastname: Priatel
authors.forename: Marc S
authors.initials: MS
authors.lastname: Horwitz
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Ziltener
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis; D007375:Interleukin-1 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D015847:Interleukin-4