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 ORCID: https://orcid.org/0000-0001-9416-2737 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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Abstract

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:	21 Oct 2022 07:31
URI:	https://orca.cardiff.ac.uk/id/eprint/100028

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