Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - CD11c depletion severely disrupts Th2 induction and development in vivo
AU - Phythian-Adams, Alexander T
AU - Cook, Peter C
AU - Lundie, Rachel J
AU - Jones, Lucy H
AU - Smith, Katherine A
AU - Barr, Tom A
AU - Hochweller, Kristin
AU - Anderton, Stephen M
AU - Hämmerling, Günter J
AU - Maizels, Rick M
AU - MacDonald, Andrew S
PY - 2010/9/27
Y1 - 2010/9/27
N2 - Although dendritic cells (DCs) are adept initiators of CD4(+) T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c-diphtheria toxin (DTx) receptor mice to deplete CD11c(+) cells during the priming stage of the CD4(+) Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c(+) DCs from all tissues tested, with 70-80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4(+) T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c(+) antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines.
AB - Although dendritic cells (DCs) are adept initiators of CD4(+) T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c-diphtheria toxin (DTx) receptor mice to deplete CD11c(+) cells during the priming stage of the CD4(+) Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c(+) DCs from all tissues tested, with 70-80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4(+) T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c(+) antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines.
KW - Animals
KW - Antigen Presentation
KW - Basophils
KW - CD11c Antigen
KW - CD4-Positive T-Lymphocytes
KW - Dendritic Cells
KW - Heparin-binding EGF-like Growth Factor
KW - Humans
KW - Intercellular Signaling Peptides and Proteins
KW - Interferon-gamma
KW - Leukocyte Reduction Procedures
KW - Lymphocyte Activation
KW - Mice
KW - Schistosoma mansoni
KW - Schistosomiasis mansoni
KW - Th2 Cells
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1084/jem.20100734
DO - 10.1084/jem.20100734
M3 - Journal article
C2 - 20819926
VL - 207
SP - 2089
EP - 2096
JO - The Journal of experimental medicine
JF - The Journal of experimental medicine
SN - 0022-1007
IS - 10
ER -