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Activation requirements for the induction of CD4+CD25+ T cell suppressor function.
Eur J Immunol 2004; 34(2):366-76EJ

Abstract

The in vivo differentiation/survival of CD4(+)CD25(+) T suppressor cells is dependent on IL-2 and CD28-mediated costimulatory signals. To determine the cytokine and costimulatory requirements for CD25(+) T cells in vitro, we established a two-stage culture system where CD25(+) T cells were activated in a primary culture. In the subsequent culture, activated CD4(+)CD25(+) cells were then mixed with responders in order to assess their suppressor function. Pre-culture of CD25(+) T cells with anti-CD3 alone resulted in poor survival and minimal induction of suppressor activity. Pre-culture in the presence of anti-CD3 and IL-2 or IL-4, but not IL-6, IL-7, IL-9, IL-10 or IL-15, resulted in proliferation of the CD25(+) cells and induction of potent suppressor function. Inhibition of the interaction of CD28 or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with CD80/CD86 in the pre-culture of CD4(+)CD25(+) cells did not prevent the induction of suppressor function. Furthermore, the inhibition of costimulatory signals did not inhibit the ability of fresh CD25(+) T cells to inhibit CD8(+) responders under conditions where activation of the responders was independent of CD80/CD86. These studies support the view that activation of CD25(+) T cells requires IL-2/IL-4 for their survival/differentiation into effector cells, but is independent of CD28/CTLA-4-mediated costimulation.

Authors+Show Affiliations

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20892-1892, USA. athornton@niaid.nih.govNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14768041

Citation

Thornton, Angela M., et al. "Activation Requirements for the Induction of CD4+CD25+ T Cell Suppressor Function." European Journal of Immunology, vol. 34, no. 2, 2004, pp. 366-76.
Thornton AM, Piccirillo CA, Shevach EM. Activation requirements for the induction of CD4+CD25+ T cell suppressor function. Eur J Immunol. 2004;34(2):366-76.
Thornton, A. M., Piccirillo, C. A., & Shevach, E. M. (2004). Activation requirements for the induction of CD4+CD25+ T cell suppressor function. European Journal of Immunology, 34(2), pp. 366-76.
Thornton AM, Piccirillo CA, Shevach EM. Activation Requirements for the Induction of CD4+CD25+ T Cell Suppressor Function. Eur J Immunol. 2004;34(2):366-76. PubMed PMID: 14768041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation requirements for the induction of CD4+CD25+ T cell suppressor function. AU - Thornton,Angela M, AU - Piccirillo,Ciriaco A, AU - Shevach,Ethan M, PY - 2004/2/10/pubmed PY - 2004/3/31/medline PY - 2004/2/10/entrez SP - 366 EP - 76 JF - European journal of immunology JO - Eur. J. Immunol. VL - 34 IS - 2 N2 - The in vivo differentiation/survival of CD4(+)CD25(+) T suppressor cells is dependent on IL-2 and CD28-mediated costimulatory signals. To determine the cytokine and costimulatory requirements for CD25(+) T cells in vitro, we established a two-stage culture system where CD25(+) T cells were activated in a primary culture. In the subsequent culture, activated CD4(+)CD25(+) cells were then mixed with responders in order to assess their suppressor function. Pre-culture of CD25(+) T cells with anti-CD3 alone resulted in poor survival and minimal induction of suppressor activity. Pre-culture in the presence of anti-CD3 and IL-2 or IL-4, but not IL-6, IL-7, IL-9, IL-10 or IL-15, resulted in proliferation of the CD25(+) cells and induction of potent suppressor function. Inhibition of the interaction of CD28 or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with CD80/CD86 in the pre-culture of CD4(+)CD25(+) cells did not prevent the induction of suppressor function. Furthermore, the inhibition of costimulatory signals did not inhibit the ability of fresh CD25(+) T cells to inhibit CD8(+) responders under conditions where activation of the responders was independent of CD80/CD86. These studies support the view that activation of CD25(+) T cells requires IL-2/IL-4 for their survival/differentiation into effector cells, but is independent of CD28/CTLA-4-mediated costimulation. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/14768041/Activation_requirements_for_the_induction_of_CD4+CD25+_T_cell_suppressor_function_ L2 - https://doi.org/10.1002/eji.200324455 DB - PRIME DP - Unbound Medicine ER -