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Regulatory T-cell depletion does not prevent emergence of new CD25+ FOXP3+ lymphocytes after antigen stimulation in culture

Melenhorst, J.J, Scheinberg, P., Lu, J., Ambrozak, D.R, Sosa, E., Zhao, L., Hensel, N.F., Savani, B.N., Douek, D.C., Price, David and Barrett, A.J. 2008. Regulatory T-cell depletion does not prevent emergence of new CD25+ FOXP3+ lymphocytes after antigen stimulation in culture. Cytotherapy 10 (2) , pp. 152-164. 10.1080/14653240701853536

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Background The removal of human regulatory T (Treg) cells from a cellular product prior to the induction of a T-cell response has the potential to boost the total yield of antigen (Ag)-specific CD4+ and CD8+ T cells. Methods We examined the effect of this manipulation on the generation of human anti-cytomegalovirus (CMV) T-cell responses. Furthermore, we examined the clonotypic composition of Ag-specific CD4+FOXP3+ and CD4+FOXP3− T cells. Results We found that the immunomagnetic depletion of CD25+ cells had an unpredictable effect on outcome, with total yields of CMV-specific T cells either increasing or decreasing after the removal of these cells. The depletion of CD25+ cells both removed a proportion of Ag-specific T cells and failed to eliminate a substantial population of Treg cells. Furthermore, using a novel T-cell receptor clonotyping technique, we found that Ag recognition induces the expression of FOXP3 in a proportion of specific T cells; these FOXP3-expressing Ag-specific CD4+ and CD8+ T cells were no longer capable of producing inflammatory cytokines. Discussion The depletion of CD25+ cells from the starting population has a variable effect on the total yield of Ag-specific T cells, a proportion of which invariably acquire FOXP3 expression and lose effector function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: CD25 depletion; cytomegalovirus; FOXP3; human; regulatory T cells; in vitro
Publisher: Elsevier
ISSN: 1465-3249
Date of First Compliant Deposit: 21 April 2017
Last Modified: 15 Mar 2018 12:23

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