2007
DOI: 10.4049/jimmunol.179.11.7295
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Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling

Abstract: Naturally occurring CD4+CD25+FoxP3+ T regulatory (Treg) cells require three distinct signals transduced via TCR, CD28, and IL-2R for their development and maintenance. These requirements served as the basis for several recently developed ex vivo expansion protocols that relied on the use of solid support-bound Abs to CD3 and CD28 in the presence of high dose IL-2. We report in this study that Treg cells up-regulate the expression of inducible costimulatory receptor 4-1BB in response to IL-2, and stimulation us… Show more

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Cited by 126 publications
(151 citation statements)
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“…CD137 can be constitutively expressed on CD4 + Foxp3 + Tregs (7,29), but whether signaling through CD137 treatment increases suppressive Treg activity, and therefore counteracting antitumor CD4 + T cell responses, is currently unknown (5,(29)(30)(31). Interestingly, we found that CD137 ligation on Tregs increases not only the size of the Treg population but also drives alterations of Treg functions to effector cells in the absence of CD8 + T cells.…”
Section: Discussionmentioning
confidence: 79%
“…CD137 can be constitutively expressed on CD4 + Foxp3 + Tregs (7,29), but whether signaling through CD137 treatment increases suppressive Treg activity, and therefore counteracting antitumor CD4 + T cell responses, is currently unknown (5,(29)(30)(31). Interestingly, we found that CD137 ligation on Tregs increases not only the size of the Treg population but also drives alterations of Treg functions to effector cells in the absence of CD8 + T cells.…”
Section: Discussionmentioning
confidence: 79%
“…46 On the contrary, these molecules as well as ICOS also facilitate the expansion of T reg cells. 36,45,47 B cells of aged BWF1 mice, however, did not show significant expression of ligands for these co-stimulatory molecules (data not shown). This observation implies that reversal of the suppression, if any, might take place through the other pathway(s).…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, several reports have now found that OX40 and 4-1BB signals can also promote proliferation and/or survival of CD4+CD25+(Foxp3+) nTreg in vitro, especially in the presence of IL-2 [27,40,41]. This suggests that an already existing CD25+Foxp3+ Treg subset might utilize these receptor/ligand systems as a means to survive and persist as a population, an action somewhat at odds with the idea that OX40 (and perhaps 4-1BB) can prevent the development of similar iTreg in the periphery.…”
Section: Ox40 and 4-1bb Support Division And Survival Of Cd25+foxp3+ mentioning
confidence: 99%