Requirements for growth and IL-10 expression of highly purified human T regulatory cells. J Clin Immunol 2012 Oct;32(5):1118-28
Date
05/09/2012Pubmed ID
22562448Pubmed Central ID
PMC4271826DOI
10.1007/s10875-012-9701-4Scopus ID
2-s2.0-84866736118 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Human regulatory T cells (T(R)) cells have potential for the treatment of a variety of immune mediated diseases but the anergic phenotype of these cells makes them difficult to expand in vitro. We have examined the requirements for growth and cytokine expression from highly purified human T(R) cells, and correlated these findings with the signal transduction events of these cells. We demonstrate that these cells do not proliferate or secrete IL-10 even in the presence of high doses of IL-2. Stimulation with a superagonistic anti-CD28 antibody (clone 9.3) and IL-2 partially reversed the proliferative defect, and this correlated with reversal of the defective calcium mobilization in these cells. Dendritic cells were effective at promoting T(R) cell proliferation, and under these conditions the proliferative capacity of T(R) cells was comparable to conventional CD4 lymphocytes. Blocking TGF-β activity abrogated IL-10 expression from these cells, while addition of TGF-β resulted in IL-10 production. These data demonstrate that highly purified populations of T(R) cells are anergic even in the presence of high doses of IL-2. Furthermore, antigen presenting cells provide proper co-stimulation to overcome the anergic phenotype of T(R) cells, and under these conditions they are highly sensitive to IL-2. In addition, these data demonstrate for the first time that TGF-β is critical to enable human T(R) cells to express IL-10.
Author List
Bonacci B, Edwards B, Jia S, Williams CB, Hessner MJ, Gauld SB, Verbsky JWAuthors
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinJames Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AntibodiesCD28 Antigens
CD3 Complex
Cell Proliferation
Dendritic Cells
Gene Expression Profiling
Humans
Interleukin-10
Interleukin-2
Monocytes
Oligonucleotide Array Sequence Analysis
T-Lymphocytes, Regulatory
Transforming Growth Factor beta