BACKGROUND: The removal of human regulatory T (T(reg)) 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 T(reg) 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.
BACKGROUND: The removal of human regulatory T (T(reg)) 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 T(reg) 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.
Authors: Robert Quan Le; J Joseph Melenhorst; Minoo Battiwalla; Brenna Hill; Sarfraz Memon; Bipin N Savani; Aarthi Shenoy; Nancy F Hensel; Eleftheria K Koklanaris; Keyvan Keyvanfar; Frances T Hakim; Daniel C Douek; A John Barrett Journal: Blood Date: 2011-03-18 Impact factor: 22.113
Authors: J Joseph Melenhorst; Ann M Leen; Catherine M Bollard; Máire F Quigley; David A Price; Cliona M Rooney; Malcolm K Brenner; A John Barrett; Helen E Heslop Journal: Blood Date: 2010-08-13 Impact factor: 22.113
Authors: J Joseph Melenhorst; Phillip Scheinberg; Ann Williams; David R Ambrozak; Keyvan Keyvanfar; Melody Smith; J Philip McCoy; Nancy F Hensel; Daniel C Douek; A John Barrett Journal: Biol Blood Marrow Transplant Date: 2011-01-06 Impact factor: 5.742
Authors: Zachariah McIver; Jan Joseph Melenhorst; Colin Wu; Andrew Grim; Sawa Ito; Irene Cho; Nancy Hensel; Minoo Battiwalla; Austin John Barrett Journal: Haematologica Date: 2012-10-12 Impact factor: 9.941
Authors: Phillip Scheinberg; Jan J Melenhorst; Jason M Brenchley; Brenna J Hill; Nancy F Hensel; Pratip K Chattopadhyay; Mario Roederer; Louis J Picker; David A Price; A John Barrett; Daniel C Douek Journal: Blood Date: 2009-09-23 Impact factor: 22.113