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Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity.
J Neurosci Res. 2003 Oct 15; 74(2):296-308.JN

Abstract

CD4+CD25+ regulatory T cells (Treg cells) prevent T cell-mediated autoimmune diseases in rodents. To develop a functional Treg assay for human blood cells, we used FACS- or bead-sorted CD4+CD25+ T cells from healthy donors to inhibit anti-CD3/CD28 activation of CD4+CD25- indicator T cells. The data clearly demonstrated classical Treg suppression of CD4+CD25- indicator cells by both CD4+CD25(+high) and CD4+CD25(+low) T cells obtained by FACS or magnetic bead sorting. Suppressive activity was found in either CD45RO- (naive) or CD45RO+ (memory) subpopulations, was independent of the TCR signal strength, required cell-cell contact, and was reversible by interleukin-2 (IL-2). Of general interest is that a wider sampling of 27 healthy donors revealed an age- but not gender-dependent loss of suppressive activity in the CD4+CD25+ population. The presence or absence of suppressive activity in CD4+CD25+ T cells from a given donor could be demonstrated consistently over time, and lack of suppression was not due to method of sorting, strength of signal, or sensitivity of indicator cells. Phenotypic markers did not differ on CD4+CD25+ T cells tested ex vivo from suppressive vs. nonsuppressive donors, although, upon activation in vitro, suppressive CD4+CD25+ T cells had significantly higher expression of both CTLA-4 and GITR than CD4+CD25- T cells from the same donors. Moreover, antibody neutralization of CTLA-4, GITR, IL-10, or IL-17 completely reversed Treg-induced suppression. Our results are highly consistent with those reported for murine Treg cells and are the first to demonstrate that suppressive activity of human CD4+CD25+ T cells declines with age.

Authors+Show Affiliations

Neuroimmunology Research and Tykeson MS Research Laboratory, Veterans Affairs Medical Center and Oregon Health and Science University, Portland, Oregon 97239, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14515359

Citation

Tsaknaridis, Laura, et al. "Functional Assay for Human CD4+CD25+ Treg Cells Reveals an Age-dependent Loss of Suppressive Activity." Journal of Neuroscience Research, vol. 74, no. 2, 2003, pp. 296-308.
Tsaknaridis L, Spencer L, Culbertson N, et al. Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. J Neurosci Res. 2003;74(2):296-308.
Tsaknaridis, L., Spencer, L., Culbertson, N., Hicks, K., LaTocha, D., Chou, Y. K., Whitham, R. H., Bakke, A., Jones, R. E., Offner, H., Bourdette, D. N., & Vandenbark, A. A. (2003). Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. Journal of Neuroscience Research, 74(2), 296-308.
Tsaknaridis L, et al. Functional Assay for Human CD4+CD25+ Treg Cells Reveals an Age-dependent Loss of Suppressive Activity. J Neurosci Res. 2003 Oct 15;74(2):296-308. PubMed PMID: 14515359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. AU - Tsaknaridis,Laura, AU - Spencer,Leslie, AU - Culbertson,Nicole, AU - Hicks,Kevin, AU - LaTocha,Dorian, AU - Chou,Yuan K, AU - Whitham,Ruth H, AU - Bakke,Antony, AU - Jones,Richard E, AU - Offner,Halina, AU - Bourdette,Dennis N, AU - Vandenbark,Arthur A, PY - 2003/9/30/pubmed PY - 2003/12/17/medline PY - 2003/9/30/entrez SP - 296 EP - 308 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 74 IS - 2 N2 - CD4+CD25+ regulatory T cells (Treg cells) prevent T cell-mediated autoimmune diseases in rodents. To develop a functional Treg assay for human blood cells, we used FACS- or bead-sorted CD4+CD25+ T cells from healthy donors to inhibit anti-CD3/CD28 activation of CD4+CD25- indicator T cells. The data clearly demonstrated classical Treg suppression of CD4+CD25- indicator cells by both CD4+CD25(+high) and CD4+CD25(+low) T cells obtained by FACS or magnetic bead sorting. Suppressive activity was found in either CD45RO- (naive) or CD45RO+ (memory) subpopulations, was independent of the TCR signal strength, required cell-cell contact, and was reversible by interleukin-2 (IL-2). Of general interest is that a wider sampling of 27 healthy donors revealed an age- but not gender-dependent loss of suppressive activity in the CD4+CD25+ population. The presence or absence of suppressive activity in CD4+CD25+ T cells from a given donor could be demonstrated consistently over time, and lack of suppression was not due to method of sorting, strength of signal, or sensitivity of indicator cells. Phenotypic markers did not differ on CD4+CD25+ T cells tested ex vivo from suppressive vs. nonsuppressive donors, although, upon activation in vitro, suppressive CD4+CD25+ T cells had significantly higher expression of both CTLA-4 and GITR than CD4+CD25- T cells from the same donors. Moreover, antibody neutralization of CTLA-4, GITR, IL-10, or IL-17 completely reversed Treg-induced suppression. Our results are highly consistent with those reported for murine Treg cells and are the first to demonstrate that suppressive activity of human CD4+CD25+ T cells declines with age. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/14515359/Functional_assay_for_human_CD4+CD25+_Treg_cells_reveals_an_age_dependent_loss_of_suppressive_activity_ L2 - https://doi.org/10.1002/jnr.10766 DB - PRIME DP - Unbound Medicine ER -