title: T lymphocyte migration to lymph nodes is maintained during homeostatic proliferation.
abstract: The immune system maintains appropriate cell numbers through regulation of cell proliferation and death. Normal tissue distribution of lymphocytes is maintained through expression of specific adhesion molecules and chemokine receptors such as L-selectin and CCR7, respectively. Lymphocyte insufficiency or lymphopenia induces homeostatic proliferation of existing lymphocytes to increase cell numbers. Interestingly, homeostatic proliferation of T lymphocytes induces a phenotypic change from naïve- to memory-type cell. Naïve T cells recirculate between blood and lymphoid tissues whereas memory T cells migrate to nonlymphoid sites such as skin and gut. To assess effects of homeostatic proliferation on migratory ability of T cells, a murine model of lymphopenia-induced homeostatic proliferation was used. Carboxyfluorescein diacetate, succinimidyl ester-labeled wild-type splenocytes were adoptively transferred into recombination activation gene-1-deficient mice and analyzed by flow cytometry, in vitro chemotactic and in vivo migration assays, and immunofluorescence microscopy. Homeostatically proliferated T cells acquired a mixed memory-type CD44high L-selectinhigh CCR7low phenotype. Consistent with this, chemotaxis to secondary lymphoid tissue chemokine in vitro was reduced by 22%-34%. By contrast, no differences were found for migration or entry into lymph nodes during in vivo migration assays. Therefore, T lymphocytes that have undergone homeostatic proliferation recirculate using mechanisms similar to naïve T cells.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, USA.
authors.forename: Masanari
authors.initials: M
authors.lastname: Kodera
authors.forename: Jamison J
authors.initials: JJ
authors.lastname: Grailer
authors.forename: Andrew P-A
authors.initials: AP
authors.lastname: Karalewitz
authors.forename: Hariharan
authors.initials: H
authors.lastname: Subramanian
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000502:physiology*; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016654:Genes, RAG-1; D006706:Homeostasis; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000166:cytology; D042601:Lymphatic Vessels / Q000166:cytology; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010641:Phenotype; D054400:Receptors, CCR7 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
chemical_list: C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054400:Receptors, CCR7