Expression of lymphotoxin-alphabeta on antigen-specific T cells is required for DC function.
During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-alphabeta (LTalphabeta) in this process because signaling through the LTbeta-receptor (LTbetaR) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs. We report that LTalphabeta is a critical participant required for optimal DC function, independent of its described role in maintaining lymphoid tissue organization. In the absence of LTalphabeta or CD40L on Ag-specific T cells, DC dysfunction could be rescued in vivo via CD40 or LTbetaR stimulation, respectively, suggesting that these two pathways cooperate for optimal DC conditioning.
Summers-DeLuca
Leslie E
LE
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
McCarthy
Douglas D
DD
Cosovic
Bojana
B
Ward
Lesley A
LA
Lo
Calvin C
CC
Scheu
Stefanie
S
Pfeffer
Klaus
K
Gommerman
Jennifer L
JL
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000378:metabolism*; D053308:Lymphotoxin-beta / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D019013:CD40 Antigens; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta