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Germinal Centers Regulate Human Th2 Development1

Johansson-Lindbom, Bengt; Ingvarsson, Sigurdur LU and Borrebaeck, Carl LU (2003) In Journal of Immunology 171(4). p.1657-1666
Abstract
In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-{gamma}, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-{gamma}-producing cells under identical culture conditions, thus establishing a correlation between... (More)
In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-{gamma}, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-{gamma}-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
171
issue
4
pages
1657 - 1666
publisher
American Association of Immunologists
external identifiers
  • pmid:12902463
  • wos:000184667400009
ISSN
1550-6606
language
English
LU publication?
yes
id
495502be-e897-4eeb-8e23-5ff74045dcdb (old id 134300)
alternative location
http://www.jimmunol.org/cgi/content/abstract/171/4/1657
date added to LUP
2007-07-05 13:15:31
date last changed
2016-04-16 04:15:14
@article{495502be-e897-4eeb-8e23-5ff74045dcdb,
  abstract     = {In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-{gamma}, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-{gamma}-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.},
  author       = {Johansson-Lindbom, Bengt and Ingvarsson, Sigurdur and Borrebaeck, Carl},
  issn         = {1550-6606},
  language     = {eng},
  number       = {4},
  pages        = {1657--1666},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Germinal Centers Regulate Human Th2 Development1},
  volume       = {171},
  year         = {2003},
}