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- Title
CTLA-4{middle dot}Ig converts naive CD4࠽ T cells into CD4࠽ regulatory T cells.
- Authors
Marjaneh Razmara; Brendan Hilliard; Azadeh K. Ziarani; Youhai H. Chen; Mark L. Tykocinski
- Abstract
CTLA-4·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·Ig, in combination with TCR ligation, has the additional capacity to convert naive CD4࠽â T cells into Foxp3 regulatory T (Treg) cells, as well as to expand their numbers. The CD4࠽맸娱ꝿ Treg generated by CTLA-4·Ig treatment in vitro potently suppress effector T cells. Extending this in vivo, we show that systemic administration of CTLA-4·Ig increases the percentage of CD4࠽릆Ⅸ욝 cells within mixed lymphocyte reaction-induced murine lymph nodes. Significantly, the in vitro conversion of naive CD4࠽â T cells into Treg 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·Ig-driven Treg induction may be predicated upon active CTLA-4·Ig to B7-2 signaling within APC, which elicits from them Treg-inducing potential. These findings extend CTLA-4·Igs 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.
- Subjects
T cells; IMMUNOSUPPRESSIVE agents; IMMUNOGLOBULINS; LYMPH nodes
- Publication
International Immunology, 2008, Vol 20, Issue 4, p471
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxn007