Gangliosides, sialic acid-containing glyco-

SummaryWe examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin- plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D- dimer, we can use these indicators to treat DIC patients at an early stage.

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We reexamined two questions concerning Lyt antigens of cytotoxic T cells of the mouse: is Lyt-1 antigen expressed on cytotoxic effector cells and can cytotoxicity be blocked by antibody to Lyt antigens in the absence of added complement? A 3-hrblCr-release assay with splenic effector cells and leukemia or myeloma target cells was used to measure cell-mediated cytotoxicity. The cytotoxic activity of effector cells against allogeneic targets was abolished by exposure to Lyt-1, Lyt-2, or Lyt-3 antiserum and complement. Specificity was established by tests with C57BL/6 Lyt congenic mice and absorption studies with thymocytes. Similarly, the cytotoxicity of effector cells directed against semisyngeneic myeloma targets was reduced by Lyt-1, -2, or -3 antiserum and complement. Effector cell cytotoxicity against another semisyngeneic target was only marginally affected by Lyt-1 antiserum and complement, but was abolished by Lyt-2 or -3 antiserum and complement. It appears likely that cytotoxic T cells are a heterogeneous population with regard to Lyt-1 expression and that past studies indicating an apparent absence of Lyt-l on cytotoxic T cells revealed a quantitative, not qualitative, feature of these cells. With regard to the activity of Lyt antisera in the absence of added complement, selective blocking of effector cell cytotoxicity for allogeneic and semisyngeneic targets was found with Lyt-2 and Lyt-3 antisera but not with Lyt-1 antiserum. The specificity of blocking was established by tests with Lyt congenic mice and absorption studies with thymocytes. With the exception of blocking by antisera to the H-2 haplotype expressed by the target cell, no effector cell blocking was observed with alloantisera or heteroantisera to a range ofother cell surface molecules present on mouse lymphoid cells. One possibility to account for the selective blocking by Lyt-2 and Lyt-3 antisera is that Lyt-2,3 determinants on the surface of cytotoxic T cells have a close spatial relation to the T cell receptor.

The molecular basis of the polymorphic tumor rejection antigens of chemically induced sarcomas of inbred mice remains a mystery, despite the discovery of these antigens over 40 years ago and their critical importance to the foundation of tumor immunology. In an analysis of a panel of BALB͞c 3-methylcholanthrene-induced tumors, we identified one tumor, CMS5, that elicited a strong cytotoxic T cell response with exquisite specificity for CMS5. A stable cloned line of T cells with this specificity (C18) was used to screen a CMS5 cDNA expression library. The gene encoding the C18-defined antigen was identified as a mutated form of a mouse mitogen-activated protein kinase, ERK2, and a peptide incorporating the resulting amino acid substitution (lysine to glutamine) was efficiently recognized by C18. Vaccination with this peptide elicited specific resistance to CMS5 challenge. Extensive efforts to isolate antigen-loss variants of CMS5 were unsuccessful, suggesting that the mutated mitogen-activated protein kinase is essential for maintenance of the malignant phenotype.