Byoung Kwon Kim

NKT cells play critical roles in the induction of oral tolerance by inducing regulatory T cells producing IL-10 and transforming growth factor β, and by clonally deleting antigen-specific T cells

Oral tolerance is the systemic unresponsiveness induced by orally administered proteins. To explore the roles of natural killer T (NKT) cells in oral tolerance, we induced oral tolerance to ovalbumin (OVA) in NKT cell‐deficient mice. In CD1d–/– mice, the induction of tolerance to orally administered high‐ or low‐dose OVA was impaired. Dendritic cells (DCs) in the Peyers patches (PPs) of CD1d–/– mice fed OVA showed high expression of major histocompatibility complex (MHC) class II and B7 molecules, whereas DCs of control mice fed OVA expressed low levels of these molecules. The adoptive transfer of NKT cells restored oral tolerance and induction of tolerogenic DCs in the PPs and spleens of CD1d–/– mice. Moreover, interleukin (IL)‐10 and transforming growth factor (TGF)‐β1 production in vitro were reduced in cells from the spleen and PPs of CD1d–/– mice compared with those of control mice fed OVA. The numbers of OVA‐specific CD4+ KJ1‐26+ T cells were significantly reduced in the PPs and spleens of DO11·10 mice fed OVA. In contrast, OVA‐specific CD4+ KJ1‐26+ T cells were not deleted in the PPs or spleens of DO11·10 CD1d–/– mice. In conclusion, NKT cells were found to play an indispensable role in oral tolerance by inducing regulatory T cells, and clonally deleting antigen‐specific CD4+ T cells.

Engagement of Glucocorticoid-Induced TNF Receptor Costimulates NKT Cell Activation In Vitro and In Vivo

Glucocorticoid-induced TNF receptor (GITR) is known to provide costimulatory signals to CD4+CD25− and CD4+CD25+ T cells during immune responses in vivo. However, the functional roles of GITR expressed on NKT cells have not been well characterized. In this study, we have explored the functions of GITR as a costimulatory factor on NKT cells. GITR was found to be constitutively expressed on NKT cells and its expression was enhanced by TCR signals. GITR engagement using DTA-1, an agonistic mAb against GITR, in the presence of TCR signals, augmented IL-2 production, the expression of activation markers, cell cycle progression, and the nuclear translocations of NF-κB p50 and p65. Furthermore, GITR engagement enhanced the production of IL-4, IL-10, IL-13, and IFN-γ by NKT cells and the expression level of phosphorylated p65 in NKT cells in the presence of TCR engagement, indicating that GITR provides costimulatory signals to NKT cells. The costimulatory effects of GITR on NKT cells were comparable to those of CD28 in terms of cytokine production. Moreover, the coinjection of DTA-1 and α-galactosylceramide into B6 mice induced more IL-4 and IFN-γ production than the coinjection of control mAbs and α-galactosylceramide. In addition, the adoptive transfer of DTA-1-pretreated NKT cells into CD1d−/− mice attenuated hypersensitivity pneumonitis more than control IgG pretreated NKT cells in these mice. These findings demonstrate that GITR engagement on NKT cells modulates immune responses in hypersensitivity pneumonitis in vivo. Taken together, our findings suggest that GITR engagement costimulates NKT cells and contributes to the regulation of immune-associated disease processes in vivo.

CD99 activates T cells via a costimulatory function that promotes raft association of TCR complex and tyrosine phosphorylation of TCR ζ

We investigated the co-stimulatory role of a cell-surface protein, CD99. Co-ligation of CD99 and suboptimal CD3 induced T-cell activation to a level comparable to that obtained with optimal CD3 or CD3+CD28. We also noted concomitant enhancement of the earliest T-cell receptor (TCR) signaling events. In addition, co-ligation of CD99 and CD3 led to translocation of TCR complexes into the lipid raft, without concomitant migration of CD99 to the raft, and consequent enhancement of TCR ζ-mediated signal 1. These data demonstrate the unique properties of CD99 co-stimulation that distinguish this molecule from CD28 and other raft-resident co-stimulatory factors.

Aneurysmal Benign Fibrous Histiocytoma with Atrophic Features

Aneurysmal benign fibrous histiocytoma is an uncommon pathologic variant of dermatofibroma. In addition to the features of a typical dermatofibroma, it has large cleft-like or cavernous blood-filled spaces with numerous hemosiderin pigments. It should be differentiated from angiomatoid malignant fibrous histiocytoma, malignant melanoma, and vascular tumors such as Kaposis sarcoma and angiosarcoma. Atrophic dermatofibroma is also a rare variant of dermatofibroma, and the combination of aneurysmal and atrophic features is rarer still. We report a case of aneurysmal benign fibrous histiocytoma with atrophic features in a 27-year-old male who had a grayish-brown atrophic patchy lesion on his back for 2 years.