IFN‐γ has been implicated in the pathogenesis of experimental cerebral malaria (ECM). We have used mice lacking the α chain of the IFN‐γ receptor (KO mice) to define its role in the pathogenesis of ECM. Infected KO mice did not develop ECM and showed no leukocyte or parasite sequestration in the brain, and no hemorrhages. The resistance of KO mice to ECM was associated with the absence of any increases of TNF‐α and ICAM‐1 proteins in the brain, which are both essential for ECM. Wild‐type (WT) mice which do not develop ECM, despite increased local production of TNF‐α protein, showed no leukocyte accumulation in the brain and this was correlated with the absence of ICAM‐1 protein from brain microvessels. KO mice infected with 106 parasitized erythrocytes (PE) of Plasmodium berghei ANKA (PbA) did not develop ECM, but they had high parasitemia and died earlier than WT mice which did not develop ECM. However, KO mice did not develop higher parasitemia than WT mice when both groups were infected with a lower dose (5×105 PE) of PbA‐infected red blood cells. This indicates that different doses of PE may trigger different IFN‐γ responses and that there may be a threshold concentration for protection against parasitemia.

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Summary Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (noninvasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.Pancreatic trypsinogen is one of the proteolytic enzymes produced by pancreatic acinar cells. A recent study (Miszczuk-Jamska et al., 1991) has shown that a new human pancreatic adenocarcinoma cell line (CFPAC-1) and a previously established human pancreatic carcinoma cell line (CAPAN-1) produce human pancreatic trypsinogen. This enzyme is a target protease for pancreatic secretory trypsin inhibitor (PSTI). Tumour-associated trypsinogen is also known to be a serine protease produced by malignant tumour cells, and is believed to play an essential role in cancer invasion and metastasis by degrading trypsin-sensitive extracellular matrix components (Tryggvason et al., 1987;Koivunen et al., 1991a). Tumour-associated trypsinogen has been identified as a target protease for a tumour-associated trypsin inhibitor (TATI), also referred to as PSTI (Huhtala et al., 1982;Halila et al., 1988;Stenman et al., 1988). A recent study (Koivunen et al., 1989) has shown that tumourassociated trypsinogen and pancreatic trypsinogen are similar with respect to amino-terminal sequence, molecular weight and immunoreactivity, but that significant differences exist with respect to isoelectrophoretic mobility and stability. Therefore, it is possible that pancreatic trypsinogen may also take part in the protease cascade associated with tumour invasion and metastasis. It is currently not known whether the differences between tumour-associated trypsinogen and pancreatic trypsinogen are a result of tissue-specific trypsinogen modification or distinct genes.We have therefore evaluated the presence or absence of pancreatic trypsinogen immunohistochemically in 23 surgically resected pancreatic ductal adeno...

A primary infection with Plasmodium chabaudi chabaudi (AS) is characterized by an expansion of gammadelta cells after the acute phase of infection in mice. This is particularly marked during chronic infections in B cell-deficient mice. Infections in gammadelta T cell-deficient mice suggest that, although these cells play some role in the control of parasitaemia and can produce interferon-gamma, they do not appear to be involved in the development of hypoglycaemia, loss of weight and temperature during a P. c. chabaudi infection. However, gammadelta T cells do influence the nature of the CD4+ T cell response during infection since, in their absence, Th2-like responses, such as interleukin (IL)-4 production and help for malaria-specific antibody responses, are more pronounced. This alteration in CD4+ T cells is reflected in a more rapid and greater immunoglobulin (Ig)G1 and IgG3 antibody response to the parasite. The large gammadelta T cell expansion normally observed in infected B cell-deficient mice did not take place in the absence of IL-2, and double-knockout mice lacking both B cells and functional IL-2 were highly susceptible to lethal infection with P. c. chabaudi. The majority of the single IL-2 knockout mice, in contrast, were able to control and clear a primary infection, suggesting that for the CD4+ T cell and antibody response, IL-2 could be replaced by other cytokines.