IL-2/ IL-2 mAb treatment generates prolonged expansion and increased cytokine production by NKT cells (50.42)

• Published in: The Journal of immunology (1950) Vol. 184; no. 1_Supplement; pp. 50 - 50.42
• Main Authors: Webster, Kylie, Kyparissoudis, Konstantinos, Godfrey, Dale, Sprent, Jonathan
• Format: Journal Article
• Language: English
• Published: 01-04-2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.50.42

Abstract
Regulatory T cells can be dramatically boosted in vivo by stimulation with a complex of IL-2 and an IL-2 mAb (JES6-1). The swift 15-fold expansion creates a tolerogenic environment that significantly perturbs autoimmunity and allograft rejection. We recently observed that IL-2/mAb treatment also expands Natural Killer T (NKT) cells, a glycolipid-specific, CD1d-restricted T cell lineage implicated in both regulatory and immunogenic responses. Interestingly, the phenotype of the IL-2/mAb-expanded NKT cells differed from those expanded with the prototypic NKT ligand, alpha-galactosylceramide (α−GalCer). The IL-2/mAb-expanded NKT cells were relatively stable and contracted slowly. They were hyper-functional, with the capacity to rapidly produce cytokines for several days after stimulation. In comparison, α−GalCer stimulated NKT cells characteristically produce a quick burst of Th1 and Th2 cytokines, an ability that then dramatically declines along with their number in the following days. Interestingly, the range of cytokines produced by IL-2/mAb-NKT cells was broad and included not only IFNγ and IL-4, but also significantly high amounts of IL-10 and IL-13. IL-17, however, was notably reduced. These variations in cytokine production appeared to alter the phenotype of dendritic cells in their vicinity. These data suggest an alternate approach to the expansion of NKT cells, specifically within the context of a regulatory milieu that may be appropriate for tolerance induction.