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ICOS-dependent extrafollicular helper T cells elicit igg production via IL-21 in systemic autoimmunity

Academic Article
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Overview

authors

  • Odegard, J. M.
  • Marks, B. R.
  • DiPlacido, L. D.
  • Poholek, A. C.
  • Kono, Dwight
  • Dong, C.
  • Flavell, R. A.
  • Craft, J.

publication date

  • November 2008

journal

  • Journal of Experimental Medicine  Journal

abstract

  • The role of specialized follicular helper T (T(FH)) cells in the germinal center has become well recognized, but it is less clear how effector T cells govern the extrafollicular response, the dominant pathway of high-affinity, isotype-switched autoantibody production in the MRL/MpJ-Fas(lpr) (MRL(lpr)) mouse model of lupus. MRL(lpr) mice lacking the Icos gene have impaired extrafollicular differentiation of immunoglobulin (Ig) G(+) plasma cells accompanied by defects in CXC chemokine receptor (CXCR) 4 expression, interleukin (IL) 21 secretion, and B cell helper function in CD4 T cells. These phenotypes reflect the selective loss of a population of T cells marked by down-regulation of P-selectin glycoprotein ligand 1 (PSGL-1; also known as CD162). PSGL-1(lo) T cells from MRL(lpr) mice express CXCR4, localize to extrafollicular sites, and uniquely mediate IgG production through IL-21 and CD40L. In other autoimmune strains, PSGL-1(lo) T cells are also abundant but may exhibit either a follicular or extrafollicular phenotype. Our findings define an anatomically distinct extrafollicular population of cells that regulates plasma cell differentiation in chronic autoimmunity, indicating that specialized humoral effector T cells akin to T(FH) cells can occur outside the follicle.

subject areas

  • Animals
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Autoimmunity
  • Cell Differentiation
  • Chemokines
  • Disease Models, Animal
  • Germinal Center
  • Immunoglobulin Class Switching
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukins
  • Lupus Erythematosus, Systemic
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Plasma Cells
  • Receptors, CXCR4
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Helper-Inducer
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Identity

PubMed Central ID

  • PMC2585848

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20080840

PubMed ID

  • 18981236
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Additional Document Info

start page

  • 2873

end page

  • 2886

volume

  • 205

issue

  • 12

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