Germinal Centers Regulate Human Th2 Development1
(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:
https://lup.lub.lu.se/record/134300
- author
- Johansson-Lindbom, Bengt ; Ingvarsson, Sigurdur LU and Borrebaeck, Carl LU
- organization
- publishing date
- 2003
- 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
- 2016-04-01 16:22:31
- date last changed
- 2018-11-21 20:40:54
@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}},
url = {{http://www.jimmunol.org/cgi/content/abstract/171/4/1657}},
volume = {{171}},
year = {{2003}},
}