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T-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3(-) conventional CD4 T cells and induction of CD4 T-cell anergy.

Eroukhmanoff, Lena LU ; Oderup, Cecilia LU and Ivars, Fredrik LU (2009) In European Journal of Immunology 39(4). p.1078-1087
Abstract
Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3x SEB) is partially due to an increased frequency of Foxp3(+) CD4 T cells. Importantly, reduced number of conventional CD25(-) Foxp3(-) cells, rather than conversion of such cells to Foxp3(+) cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3x OVA) and OVA-peptide (OVAp) (3x OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3x OVAp and 3x SEB mice. However, the in vivo... (More)
Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3x SEB) is partially due to an increased frequency of Foxp3(+) CD4 T cells. Importantly, reduced number of conventional CD25(-) Foxp3(-) cells, rather than conversion of such cells to Foxp3(+) cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3x OVA) and OVA-peptide (OVAp) (3x OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3x OVAp and 3x SEB mice. However, the in vivo anergy was CD4 T-cell autonomous and independent of Foxp3(+) Treg. Finally, proliferation of transferred CD4 T cells was inhibited in repeatedly immunized mice but inhibition was lost when transfer was delayed, despite the maintenance of elevated frequency of Foxp3(+) cells. These data provide important implications for Foxp3(+) cell-mediated tolerance in situations of repeated antigen exposure such as human persistent infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Immunology
volume
39
issue
4
pages
1078 - 1087
publisher
John Wiley & Sons
external identifiers
  • wos:000265478700018
  • pmid:19283777
  • scopus:65449129320
ISSN
1521-4141
DOI
10.1002/eji.200838653
language
English
LU publication?
yes
id
ef50158b-3abf-4920-99eb-20c583bdab49 (old id 1367833)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19283777?dopt=Abstract
date added to LUP
2009-07-09 13:33:12
date last changed
2017-07-30 03:36:20
@article{ef50158b-3abf-4920-99eb-20c583bdab49,
  abstract     = {Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3x SEB) is partially due to an increased frequency of Foxp3(+) CD4 T cells. Importantly, reduced number of conventional CD25(-) Foxp3(-) cells, rather than conversion of such cells to Foxp3(+) cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3x OVA) and OVA-peptide (OVAp) (3x OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3x OVAp and 3x SEB mice. However, the in vivo anergy was CD4 T-cell autonomous and independent of Foxp3(+) Treg. Finally, proliferation of transferred CD4 T cells was inhibited in repeatedly immunized mice but inhibition was lost when transfer was delayed, despite the maintenance of elevated frequency of Foxp3(+) cells. These data provide important implications for Foxp3(+) cell-mediated tolerance in situations of repeated antigen exposure such as human persistent infections.},
  author       = {Eroukhmanoff, Lena and Oderup, Cecilia and Ivars, Fredrik},
  issn         = {1521-4141},
  language     = {eng},
  number       = {4},
  pages        = {1078--1087},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {T-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3(-) conventional CD4 T cells and induction of CD4 T-cell anergy.},
  url          = {http://dx.doi.org/10.1002/eji.200838653},
  volume       = {39},
  year         = {2009},
}