Changes in the lymph node microenvironment induced by oncostatin M.
Oncostatin M (OM) transforms the lymph node (LN) into a "super lymphoid organ" with 2 striking features: massive thymus-independent T-cell development and major expansion of the memory T-cell pool. We report that T-cell development in the LckOM LN is regulated by a cyclooxygenase-2 (COX-2)-dependent neoangiogenesis involving high endothelial venules (HEVs). That LN HEVs are particularlyrich in OM-receptor beta-chain provides aplausible explanation for the fact that extrathymic T-cell development in LckOM mice is limited to the LN. Moreover, we found that increased production of the CCL20 chemokine by LN stromal cells was instrumental in the expansion of the memory phenotype CD4 T-cell pool in LckOM mice. The generality of the latter finding was demonstrated by the fact that CCL20/CCR6 interactions increase the basal proliferation rate of CD62L(lo) CD4 T cells irrespective of their thymic (in non-OM-transgenic mice) or extrathymic (in LckOM mice) origin. To our knowledge, CCL20 is the first molecule found to increase the proliferation of memory phenotype CD4 T cells. These findings identify potential targets for the creation of thymic substitutes (LN HEVs) and for expansion of the CD4 memory T-cell compartment (CCL20).
Louis
Isabelle
I
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada.
Dulude
Gaël
G
Corneau
Sophie
S
Brochu
Sylvie
S
Boileau
Catherine
C
Meunier
Caroline
C
Côté
Caroline
C
Labrecque
Nathalie
N
Perreault
Claude
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D054418:Chemokine CCL20; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007156:Immunologic Memory / Q000502:physiology; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology; D053683:Oncostatin M; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D015851:Interleukin-7; D007527:Isoenzymes; D019402:Macrophage Inflammatory Proteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D053683:Oncostatin M; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases