Inhibition of human CD4(+)CD25(+high) regulatory T cell function

• Published in: The Journal of immunology (1950) Vol. 169; no. 11; pp. 6210 - 6217
• Main Authors: Baecher-Allan, Clare, Viglietta, Vissia, Hafler, David A
• Format: Journal Article
• Language: English
• Published: United States 01-12-2002
• Subjects: Antigens; CD4-Positive T-Lymphocytes - immunology; Coculture Techniques; Cytokines - biosynthesis; Glucocorticoid-Induced TNFR-Related Protein; Humans; Immune Tolerance; Interleukin-10 - biosynthesis; Lymphocyte Activation; Models, Immunological; Receptors, Interleukin-2 - metabolism; Receptors, Nerve Growth Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Signal Transduction; T-Lymphocyte Subsets - immunology; Transforming Growth Factor beta - antagonists & inhibitors
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.169.11.6210

CD4(+)CD25(+high) T cells are potent regulators of autoreactive T cells. However, it is unclear how regulatory CD4(+)CD25(+high) cells discriminate between desirable inflammatory immune responses to microbial Ags and potentially pathologic responses by autoreactive T cells. In this study, an in vitro model was created that allowed differential activation of regulatory CD4(+)CD25(+high) and responder CD4(+) T cells. If CD4(+)CD25(+high) regulatory cells were strongly activated, they maintained suppressive effector function for only 15 h, while stimulation with weaker TCR stimuli produced regulatory cells that were suppressive until 60 h after activation. In contrast, strongly activated CD4(+) responder T cells were resistant to regulation at all time points, while weakly stimulated CD4(+) cells were sensitive to suppression until 38 or 60 h after activation depending upon the strength of the stimulus. The extent of suppression mediated by CD4(+)CD25(+high) cells also depended on the strength of stimulation in an Ag-specific system. Thus, the stronger the TCR signal, the more rapidly and more completely the responder cells become refractory to suppression.