Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 3, Pages 640-646Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200737529
Keywords
antigen stimulation; cAMP; CD8(+)CD25(+); adaptive regulatory; T cells; human
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Continuous antigen stimulation of CD4(+)CD25(-) T cells leads to generation of adaptive CD4(+)CD25(+)FOXP3(+) regulatory T (TR) cells. Here, we show that highly suppressive adaptive CD8(+)CD25(+)FOXP3(+) T cells can be generated in the same manner by continuous antigen stimulation in the presence of CD14(+) monocytes. During the course of stimulation, acquisition of immunosuppressive properties develops in parallel with up-regulation and expression of cytotoxic molecules. The CD8(+) TR cells inhibit CD4(+) and CD8(+) T cell proliferation and cytokine production, but do not alter the expression of granzyme A and granzyme B or perforin in CD8(+) effector T cells. Although, the CD8(+) TR cells express prostaglandin E-2, IL-10 and TGF-beta, the mechanism of suppression was independent of these soluble factors. In contrast to adaptive CD4(+) T-R cells, the CD8(+) TR cells suppress mainly by a contact-dependent mechanism as evident from transwell experiments. However, neither blocking antibodies to CTLA-4, CD80 nor CD86 could reverse CD8(+) T-R-mediated suppression, indicating that other mechanism(s) must be employed by these cells.
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