T-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3(-) conventional CD4 T cells and induction of CD4 T-cell anergy.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1367833
- author
- Eroukhmanoff, Lena LU ; Oderup, Cecilia LU and Ivars, Fredrik LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Immunology
- volume
- 39
- issue
- 4
- pages
- 1078 - 1087
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000265478700018
- pmid:19283777
- scopus:65449129320
- pmid:19283777
- 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
- 2016-04-01 11:49:16
- date last changed
- 2022-02-18 05:52:03
@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 Inc.}}, 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}}, doi = {{10.1002/eji.200838653}}, volume = {{39}}, year = {{2009}}, }