ABSTRACT
Two-signal models are useful in explaining various types of immune responses. In particular, secondary, so-called costimulatory, signals are critically required for the process of T-cell activation, survival, differentiation, and memory formation. Early studies in rodent models showed that targeting T-cell costimulatory pathways elicits immunological tolerance, providing a basis for development of costimulatory therapeutics in allograft rejection. However, as the classic definition of T-cell costimulation continues to evolve, simple blockade of costimulatory pathways has limitations in prevention of allograft rejection. Furthermore, functions of costimulatory molecules are much more diverse than initially anticipated and beyond T cells. In this mini-review, we will discuss CD137-CD137L bidirectional signals as examples showing that two-signals can be applicable to multiple phases of immune responses.
Subject(s)
Adaptive Immunity , Allografts , Memory , Rodentia , T-LymphocytesABSTRACT
Although the majority of research on CD137 has been directed to T cells, it is becoming clear that this molecule has distinct functions in other lineages of cells, including non-hematopoietic cells. In particular, emerging evidence suggests that the CD137-its ligand (CD137L) network involving immune cells and non-immune cells, directly or indirectly regulates inflammation in both positive and negative manners. Bidirectional signaling through both CD137 and CD137L is critical in the evolution of inflammation: 1) CD137L signaling plays an indispensible role in the activation and recruitment of neutrophils by inducing the production of proinflammatory cytokines and chemokines in hematopoietic and non-hematopoietic cells such as macrophages, endothelial cells and epithelial cells; 2) CD137 signaling in NK cells and T cells is required for their activation and can influence other cells participating in inflammation via either their production of proinflammatory cytokines or engagement of CD137L by their cell surface CD137: 3) CD137 signaling can suppress inflammation by controlling regulatory activities of dendritic cells and regulatory T cells. As recognition grows of the role of dysregulated CD137 or CD137L stimulation in inflammatory diseases, significant efforts will be needed to develop antagonists to CD137 or CD137L.
Subject(s)
Chemokines , Cytokines , Dendritic Cells , Endothelial Cells , Inflammation , Killer Cells, Natural , Macrophages , Neutrophils , T-Lymphocytes , T-Lymphocytes, RegulatoryABSTRACT
Objective:To study the expression of CD137L in laryngeal carcinoma, and to analyze its clinicopathological significance.Method:The expression of CD137L in 50 laryngeal carcinoma specimens and 9 normal laryngeal mucous tissues were detected by immunohistochemical staining.Result:The positive CD137L staining were found in all 50 cases of laryngeal carcinomas (100%), while its staining were negative in normal laryngeal mucous. There was significant difference between two groups(P<0.01). The positive ratio of CD137L staining had no relationship with the factors such as age, sex and tumor site, while it had significant correlation with the pathological stage,T stage and lymph node metastasis.Conclusion:The expression of CD137L might play an important role in the development of laryngeal carcinomas.
ABSTRACT
[Objective] To detect the expression of CD137L mRNA and protein in colorectal cancer tissues and discuss its possible clinical significance.[Methods] To detect the expression of CD137L mRNA in colorectal cancer tissues and adjacent noncancerous tissues by real-time RT-PCR and immunohistochemistry and to analyze the relationship between CD137L expression and clinical features.[Results] The mean level of CD137L mRNA in colorectal cancer tissues is significantly higher than that of adjacent noncancerous tissues (0.035 ± 0.013 vs.0.008 ± 0.005,P ＜ 0.05 ).CD137L mRNA expression in colorectal cancer show no significant differences among different age,sex,tumor location,Dukes classification,histological differentiation,and serum levels of CEA.We selected 8 colorectal cancer tissues and 3 adjacent tissues randomly to analyze the expression of CD137L by immunohistochemistry.CD137L was expressed on tumor cells in colorectal cancer tissues.The expression of CD137L was observed only in colorectal cancer tissues (6/8),but not in adjacent noncancerous tissues (0/3).[Conclusions] The expression of CD137L Mrna in colorectal cancer tissues is higher than that of adjacent noncancerous tissues and CD137 is expressed on tumor cell surface,it might be of biological importance for the progression of colorectal cancer.