NKG2D Enhances Double-Negative T Cell Regulation of B Cells.

Numerous studies reported a small subpopulation of TCRαß+CD4-CD8- (double-negative) T cells that exert regulatory functions in the peripheral lymphocyte population. However, the origin of these double-negative T (DNT) cells is controversial. Some researchers reported that DNT cells originated from the thymus, and others argued that these cells are derived from peripheral immune induction. We report a possible mechanism for the induction of nonregulatory CD4+ T cells to become regulatory double-negative T (iDNT) cells in vitro. We found that immature bone marrow dendritic cells (CD86+MHC-II- DCs), rather than mature DCs (CD86+MHC-II+), induced high levels of iDNT cells. The addition of an anti-MHC-II antibody to the CD86+MHC-II+ DC group significantly increased induction. These iDNT cells promoted B cell apoptosis and inhibited B cell proliferation and plasma cell formation. A subgroup of iDNT cells expressed NKG2D. Compared to NKG2D- iDNT cells, NKG2D+ iDNT cells released more granzyme B to enhance B cell regulation. This enhancement may function via NKG2D ligands expressed on B cells following lipopolysaccharide stimulation. These results demonstrate that MHC-II impedes induction, and iDNT cells may be MHC independent. NKG2D expression on iDNT cells enhanced the regulatory function of these cells. Our findings elucidate one possible mechanism of the induction of peripheral immune tolerance and provide a potential treatment for chronic allograft rejection in the future.

Surgical treatment of intrahepatic cholangiocarcinoma: a retrospective study of 104 cases.

OBJECTIVE: To explore the clinicopathological features, surgical treatment techniques, and prognostic risk factors of intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 104 ICC cases were collected from January 2008 to December 2013 at Tianjin Medical University Cancer Institute and Hospital and divided into the hepatic hilum lymphadenectomy (HLL, 21 cases), extended hepatic hilum lymphadenectomy (EHLL, 12 cases), and non-lymphadenectomy (NL, 71 cases) groups. The clinical data of the patients were retrospectively analyzed, and the prognostic differences were compared among different groups. RESULTS: The 1-, 2-, and 3-year overall survival (OS) rates of all cases were 72.1%, 56.1%, and 43.7%, respectively. The median survival duration was 34 months. The 1-, 2-, and 3-year OS rates of the HLL group (42.9%, 28.6%, and 28.6%, respectively) were significantly lower than those of the NL group (78.9%, 62.5%, and 47.8%, respectively). Meanwhile, the 1-, 2-, and 3-year OS rates of the EHLL group (75.0%, 56.1%, and 33.3%, respectively) were not significantly different from those of the other two groups. Univariate analysis showed that age, gender, American Joint Committee on Cancer (AJCC) stage, differentiation, ferritin (Fer), carbohydrate antigen19-9 (CA19-9) and carcinoembryonicantigen (CEA) levels, lymph node metastasis (LNM), and lymph node dissection (LND) were prognostic factors for the long-term survival of ICC. Meanwhile, multivariate analysis revealed that age, AJCC stage, differentiation, Fer levels, and LNM were independent risk factors for survival. CONCLUSIONS: ICC patients will not benefit from lymphadenectomy in the absence of LNM. However, systematic lymphadenectomy may improve ICC outcomes if the location of lymphatic metastasis is known. Age, AJCC stage, differentiation, Fer level, and LNM are independent risk factors for survival in ICC.