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CTLA-4 x Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells.
Int Immunol. 2008 Apr; 20(4):471-83.II

Abstract

CTLA-4 x Ig was originally designed as an immunosuppressive agent capable of interfering with the co-stimulation of T cells. In the present study, we demonstrate that CTLA-4 x Ig, in combination with TCR ligation, has the additional capacity to convert naive CD4+CD25- T cells into Foxp3+ regulatory T (T(reg)) cells, as well as to expand their numbers. The CD4+CD25+Foxp3+ T(reg) generated by CTLA-4 x Ig treatment in vitro potently suppress effector T cells. Extending this in vivo, we show that systemic administration of CTLA-4 x Ig increases the percentage of CD4+CD25(hi)Foxp3+ cells within mixed lymphocyte reaction-induced murine lymph nodes. Significantly, the in vitro conversion of naive CD4+CD25- T cells into T(reg) cells is antigen-presenting cell (APC) dependent. This finding, together with the further observation that this conversion can also be driven in vitro by an antibody that engages B7-2 ligand, suggests that CTLA-4 x Ig-driven T(reg) induction may be predicated upon active CTLA-4 x Ig to B7-2 signaling within APC, which elicits from them T(reg)-inducing potential. These findings extend CTLA-4 x Ig's functional repertoire, and at the same time, reinforce the concept that T cell anergy and active suppression are not entirely distinct processes and may be linked by some common molecular triggers.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18272926

Citation

Razmara, Marjaneh, et al. "CTLA-4 X Ig Converts Naive CD4+CD25- T Cells Into CD4+CD25+ Regulatory T Cells." International Immunology, vol. 20, no. 4, 2008, pp. 471-83.
Razmara M, Hilliard B, Ziarani AK, et al. CTLA-4 x Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells. Int Immunol. 2008;20(4):471-83.
Razmara, M., Hilliard, B., Ziarani, A. K., Chen, Y. H., & Tykocinski, M. L. (2008). CTLA-4 x Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells. International Immunology, 20(4), 471-83. https://doi.org/10.1093/intimm/dxn007
Razmara M, et al. CTLA-4 X Ig Converts Naive CD4+CD25- T Cells Into CD4+CD25+ Regulatory T Cells. Int Immunol. 2008;20(4):471-83. PubMed PMID: 18272926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CTLA-4 x Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells. AU - Razmara,Marjaneh, AU - Hilliard,Brendan, AU - Ziarani,Azadeh K, AU - Chen,Youhai H, AU - Tykocinski,Mark L, Y1 - 2008/02/13/ PY - 2008/2/15/pubmed PY - 2008/9/9/medline PY - 2008/2/15/entrez SP - 471 EP - 83 JF - International immunology JO - Int. Immunol. VL - 20 IS - 4 N2 - CTLA-4 x Ig was originally designed as an immunosuppressive agent capable of interfering with the co-stimulation of T cells. In the present study, we demonstrate that CTLA-4 x Ig, in combination with TCR ligation, has the additional capacity to convert naive CD4+CD25- T cells into Foxp3+ regulatory T (T(reg)) cells, as well as to expand their numbers. The CD4+CD25+Foxp3+ T(reg) generated by CTLA-4 x Ig treatment in vitro potently suppress effector T cells. Extending this in vivo, we show that systemic administration of CTLA-4 x Ig increases the percentage of CD4+CD25(hi)Foxp3+ cells within mixed lymphocyte reaction-induced murine lymph nodes. Significantly, the in vitro conversion of naive CD4+CD25- T cells into T(reg) cells is antigen-presenting cell (APC) dependent. This finding, together with the further observation that this conversion can also be driven in vitro by an antibody that engages B7-2 ligand, suggests that CTLA-4 x Ig-driven T(reg) induction may be predicated upon active CTLA-4 x Ig to B7-2 signaling within APC, which elicits from them T(reg)-inducing potential. These findings extend CTLA-4 x Ig's functional repertoire, and at the same time, reinforce the concept that T cell anergy and active suppression are not entirely distinct processes and may be linked by some common molecular triggers. SN - 1460-2377 UR - https://www.unboundmedicine.com/medline/citation/18272926/CTLA_4_x_Ig_converts_naive_CD4+CD25__T_cells_into_CD4+CD25+_regulatory_T_cells_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxn007 DB - PRIME DP - Unbound Medicine ER -