T lymphocytes negatively regulate lymph node lymphatic vessel formation.
Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, we show that LNLV formation was negatively regulated by T cells. In both steady and inflammatory states, the density of LNLVs was increased in the absence of T cells but decreased when T cells were restored. Interferon-γ secretion by T cells suppressed lymphatic-specific genes in lymphatic endothelial cells and consequently caused marked reduction in LNLV formation. When T cells were depleted, recruitment of antigen-carrying DCs to LNs was augmented, reflecting a compensatory mechanism for antigen presentation to T cells through increased LNLVs. Thus, T cells maintain the homeostatic balance of LNLV density through a negative paracrine action of interferon-γ.
National Research Laboratory of Vascular Biology, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
Raghu P
RP
Kataru
Honsoul
H
Kim
Cholsoon
C
Jang
Dong Kyu
DK
Choi
Bong Ihn
BI
Koh
Minah
M
Kim
Sudheer
S
Gollamudi
Yun-Keun
YK
Kim
Seung-Hyo
SH
Lee
Gou Young
GY
Koh
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D025461:Feedback, Physiological; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000235:genetics; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D019899:Paracrine Communication / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D007371:Interferon-gamma