Activation of the cell-surface antigen CD95 induces apoptosis of CD95-bearing tumor cells. In this study, we investigated the antitumor effect of locally produced CD95 ligand (CD95L) on CD95-negative tumor cells in vivo. Introduction of CD95L cDNA into murine tumor cells did not affect growth in vitro but caused rejection in vivo. Neutrophils were primarily responsible for this rejection. A CD8 T cell-mediated protective immunity against subsequent challenge with parental tumor cells was also elicited. These results provide evidence for the potential utility of CD95L in tumor eradication and also reveal a proinflammatory function of CD95L.

Together, these findings indicate that V␣14͞V␤8.2 is a unique antigen receptor for NKT cells but not for conventional T cells. Because V␣14 NKT cell development was inhibited largely in mice that lack the MHC class I-like molecule CD1d, positive selection of V␣14-expressing immature NKT cells requires CD1d expression (14,15). Recently, it has been shown that glycolipid, ␣-galactosylceramide (␣-GalCer), and glycosylphosphatidylinositol-anchored proteins can be presented by murine CD1d (13, 16). Subsequently, it was demonstrated that NKT cells can recognize cellular lipids or purified phospholipids distinct from ␣-GalCer (17).Although physiological functions of NKT cells remain obscure, some studies have suggested that NKT cells can control autoimmune diseases (18-21) and Th1͞Th2 cell development Here, we have evaluated the role of V␣14 NKT cells in allograft rejection and tolerance by using a murine model of transplantation. We found that V␣14 NKT cells play a critical role in the induction of vascularized cardiac allograft tolerance by blockade of lymphocyte function-associated antigen-1 (LFA-1)͞intercellular adhesion molecule-1 (ICAM-1) or CD28͞B7 interactions. Possible mechanisms for the tolerogenic function of V␣14 NKT cells are examined. Materials and Methods mAbs and Reagents.Hybridomas producing anti-LFA-1 and anti-ICAM-1 mAbs (KBA and KAT-1, respectively) were described previously (32, 33). Hybridomas producing anti-B7-1 and anti-B7-2 mAbs (1G10 and GL1, respectively) were purchased from American Type Culture Collection (ATCC). Hybridoma producing anti-IL-4 mAb (11B11) also was purchased from ATCC. These mAbs were purified from ascites by using protein G column. mAbs against CD1d (1B1) and H-2K b (AF6-88.5, FITC-labeled) were purchased from PharMingen. An annexin V PE staining kit was purchased from PharMingen.

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A surgical specimen was obtained from a patient (female, 73 years old) who was diagnosed with lung adenocarcinoma (mixed subtypes) and underwent pulmonary lobe resection at the Department of Cardiovascular and Thoracic Surgery, Hokkaido University Hospital in 2015. The patient did not undergo any preoperative chemotherapy or radiotherapy. The resected lung cancer tissues (~1.0 cm 3 without necrosis) were put into ice-cold RPMI-1640 supplemented with 10% fetal bovine serum (HyClone, GE Healthcare), 0.1 mM non-essential amino acids (Gibco), 100 IU/ml penicillin and 100 μg/ml streptomycin (Gibco) and 0.03% glutamine (Gibco), and transported immediately to the lab. After the removal of blood clots, the sample was rinsed with sterile PBS and cut into small fragments (~1 mm 3

Human invariant Vα24+ NKT cells are a relatively new subpopulation of lymphocytes. It has been reported that Vα24 NKT cells are significantly involved in some human diseases. We have evaluated the number and function of Vα24 NKT cells in both healthy volunteers and cancer patients. In this study we found that Vα24 NKT cells in unfractionated PBMCs obtained from cancer patients did not respond efficiently to α-galactosylceramide (α-GalCer) in vitro. Thus, their proportion after stimulation with α-GalCer was smaller than that found in healthy volunteers. However, the cancer patients’ Vα24 NKT cells retained cytotoxic activity against malignant target cells, and they could efficiently proliferate to α-GalCer when fractionated by sorting. Furthermore, we found that addition of G-CSF to the culture could restore the low proliferative response of Vα24 NKT cells from cancer patients. These results suggest that some functions of NKT cells in cancer patients are impaired, and this observation carries significant implications for immunotherapy-based cancer treatments.

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Natural killer T (NKT) cells are a population of autoreactive cells that mediate both protective and regulatory immune functions. NKT cells comprise several subsets of cells, but it has been unclear whether these different NKT cell subsets possess distinct functions in vivo. New studies now demonstrate that subsets of NKT cells are indeed functionally distinct and that the specific functions of these cells may be dictated in part by organ-specific mechanisms.