Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy
In addition to CD4+ regulatory T cells (Tregs), CD8+ suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8+ T cells with suppressive activities have been described. Among them, a small population of CD8+CD25+FOXP3+ T cells is found both in mice and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00171/full |
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| author | Guillaume eChurlaud Guillaume eChurlaud Guillaume eChurlaud fabien epitoiset fabien epitoiset fabien epitoiset fadi ejebbawi fadi ejebbawi roberta elorenzon roberta elorenzon roberta elorenzon bertrand ebellier bertrand ebellier michelle erosenzwajg michelle erosenzwajg michelle erosenzwajg David eKlatzmann David eKlatzmann David eKlatzmann |
| author_facet | Guillaume eChurlaud Guillaume eChurlaud Guillaume eChurlaud fabien epitoiset fabien epitoiset fabien epitoiset fadi ejebbawi fadi ejebbawi roberta elorenzon roberta elorenzon roberta elorenzon bertrand ebellier bertrand ebellier michelle erosenzwajg michelle erosenzwajg michelle erosenzwajg David eKlatzmann David eKlatzmann David eKlatzmann |
| author_sort | Guillaume eChurlaud |
| collection | DOAJ |
| description | In addition to CD4+ regulatory T cells (Tregs), CD8+ suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8+ T cells with suppressive activities have been described. Among them, a small population of CD8+CD25+FOXP3+ T cells is found both in mice and humans. In contrast to thymic-derived CD4+CD25+FOXP3+ Tregs, their origin and their role in the pathophysiology of autoimmune diseases (AIDs) are less understood. We report here the number, phenotype and function of CD8+ Tregs cells in mice and humans, at the steady state and in response to low-dose interleukin-2 (IL-2). CD8+ Tregs represent approximately 0.4 and 0.1% of peripheral blood T cells in healthy humans and mice, respectively. In mice, their frequencies are quite similar in lymph nodes and the spleen, but 2- to 3-fold higher in Peyer patches and mesenteric lymph nodes. CD8+ Tregs express low levels of CD127. CD8+ Tregs express more activation or proliferation markers such as CTLA-4, ICOS, and Ki67 than other CD8+ T cells. In vitro, they suppress effector T cell proliferation as well as or even better than CD4+ Tregs. Owing to constitutive expression of CD25, CD8+ Tregs are 20- to 40-fold more sensitive to in vitro IL-2 stimulation than CD8+ effector T cells, but 2-4 times less than CD4+ Tregs. Nevertheless, low-dose IL-2 dramatically expands and activates CD8+ Tregs even more than CD4+ Tregs, in mice and humans. Further studies are warranted to fully appreciate the clinical relevance of CD8+ Tregs in AIDs and the efficacy of IL-2 treatment. |
| first_indexed | 2024-12-11T21:57:22Z |
| format | Article |
| id | doaj.art-56f166e106864ee99fde552415977104 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T21:57:22Z |
| publishDate | 2015-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-56f166e106864ee99fde5524159771042022-12-22T00:49:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-04-01610.3389/fimmu.2015.00171128378Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapyGuillaume eChurlaud0Guillaume eChurlaud1Guillaume eChurlaud2fabien epitoiset3fabien epitoiset4fabien epitoiset5fadi ejebbawi6fadi ejebbawi7roberta elorenzon8roberta elorenzon9roberta elorenzon10bertrand ebellier11bertrand ebellier12michelle erosenzwajg13michelle erosenzwajg14michelle erosenzwajg15David eKlatzmann16David eKlatzmann17David eKlatzmann18AP-HP, Pitié-Salpêtrière hospitalSorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959AP-HP, Pitié-Salpêtrière hospitalSorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959Sorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959AP-HP, Pitié-Salpêtrière hospitalSorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959Sorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959AP-HP, Pitié-Salpêtrière hospitalSorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959AP-HP, Pitié-Salpêtrière hospitalSorbonne Université, UPMC Univ Paris 06, UMRS 959INSERM, UMR_S 959In addition to CD4+ regulatory T cells (Tregs), CD8+ suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8+ T cells with suppressive activities have been described. Among them, a small population of CD8+CD25+FOXP3+ T cells is found both in mice and humans. In contrast to thymic-derived CD4+CD25+FOXP3+ Tregs, their origin and their role in the pathophysiology of autoimmune diseases (AIDs) are less understood. We report here the number, phenotype and function of CD8+ Tregs cells in mice and humans, at the steady state and in response to low-dose interleukin-2 (IL-2). CD8+ Tregs represent approximately 0.4 and 0.1% of peripheral blood T cells in healthy humans and mice, respectively. In mice, their frequencies are quite similar in lymph nodes and the spleen, but 2- to 3-fold higher in Peyer patches and mesenteric lymph nodes. CD8+ Tregs express low levels of CD127. CD8+ Tregs express more activation or proliferation markers such as CTLA-4, ICOS, and Ki67 than other CD8+ T cells. In vitro, they suppress effector T cell proliferation as well as or even better than CD4+ Tregs. Owing to constitutive expression of CD25, CD8+ Tregs are 20- to 40-fold more sensitive to in vitro IL-2 stimulation than CD8+ effector T cells, but 2-4 times less than CD4+ Tregs. Nevertheless, low-dose IL-2 dramatically expands and activates CD8+ Tregs even more than CD4+ Tregs, in mice and humans. Further studies are warranted to fully appreciate the clinical relevance of CD8+ Tregs in AIDs and the efficacy of IL-2 treatment.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00171/fullAutoimmunityImmunotherapyimmune responseimmunological toleranceT cell biology |
| spellingShingle | Guillaume eChurlaud Guillaume eChurlaud Guillaume eChurlaud fabien epitoiset fabien epitoiset fabien epitoiset fadi ejebbawi fadi ejebbawi roberta elorenzon roberta elorenzon roberta elorenzon bertrand ebellier bertrand ebellier michelle erosenzwajg michelle erosenzwajg michelle erosenzwajg David eKlatzmann David eKlatzmann David eKlatzmann Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy Frontiers in Immunology Autoimmunity Immunotherapy immune response immunological tolerance T cell biology |
| title | Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy |
| title_full | Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy |
| title_fullStr | Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy |
| title_full_unstemmed | Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy |
| title_short | Human and mouse CD8+CD25+FOXP3+ regulatory T cells at steady state and during interleukin-2 therapy |
| title_sort | human and mouse cd8 cd25 foxp3 regulatory t cells at steady state and during interleukin 2 therapy |
| topic | Autoimmunity Immunotherapy immune response immunological tolerance T cell biology |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00171/full |
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