The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo

J Immunol. 2005 Aug 15;175(4):2340-8. doi: 10.4049/jimmunol.175.4.2340.

Abstract

ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We examined the contribution of ICOS/B7RP-1 to the generation of CXCR5+ follicular B helper T (T(FH)) cells in vivo, which preferentially migrate to the B cell zone where they provide cognate help to B cells. In the spleen, anti-B7RP-1 mAb-treated or ICOS-deficient mice showed substantially impaired development of CXCR5+ T(FH) cells and peanut agglutinin+ germinal center B cells in response to primary or secondary immunization with SRBC. Expression of CXCR5 on CD4+ T cells was associated with ICOS expression. Adoptive transfer experiments showed that the development of CXCR5+ T(FH) cells was enhanced by interaction with B cells, which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5+ T(FH) cells in the lymph nodes was also inhibited by the anti-B7RP-1 mAb treatment. These results indicated that the ICOS/B7RP-1 interaction plays an essential role in the development of CXCR5+ T(FH) cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / genetics
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B7-1 Antigen / immunology
  • CD28 Antigens / genetics
  • CD28 Antigens / physiology
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Chemokines, CXC / metabolism
  • Female
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Immunization, Secondary
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Membrane Glycoproteins / immunology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, Knockout
  • Mice, SCID
  • OX40 Ligand
  • Receptors, CXCR5
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Cytokine / biosynthesis*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / genetics
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factors

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • B7-1 Antigen
  • CD28 Antigens
  • CD40 Antigens
  • CXCR5 protein, mouse
  • Chemokines, CXC
  • ICOS protein, human
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Membrane Glycoproteins
  • Membrane Proteins
  • OX40 Ligand
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNFRSF4 protein, human
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factors