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 -