Search

Modulatory effect on the murine self defense system by a newly discovered acidic polysaccharide (ANK-102) produced by P. tuberosa cells in liquid culture was examined. Pretreatment with ANK-102 deteriorated the murine survival against lethal infection of Listeria monocytogenes, an intracellular gram-positive bacterium eliminated mainly by macrophages through T-cell mediated immune response. Pretreatment with ANK-102 resulted in the accumulation of Mac 1 and Mac 2 positive cells in the peritoneal cavity of the infected animals and the reduction of Thy1.2 expression on the surface of the thymocytes. A new type of immunosuppressive polysaccharide ANK-102 was introduced.

The defective antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNC) from patients with leukocyte adhesion deficiency (LAD), beta 2 integrins (CD11a-c/CD18) deficiency was shown. LAD patients completely failed to generate MNC-ADCC against sheep red blood cells (SRBC) sensitized with murine (m) IgG2b, but had diminished but significant cytolysis against mIgG2a-SRBC, suggesting that the CD11/CD18 requirement of Fc gamma RI is different from that of Fc gamma RII in MNC-ADCC. Blocking experiments with monoclonal antibodies (mAb) against individual subunits of CD11/CD18 revealed that anti-CD18 mAb almost completely inhibited mIgG2b-mediated ADCC by normal monocytes, but only partially inhibited mIgG2a-mediated ADCC. These data may confirm the evidence that Fc gamma RII-mediated ADCC absolutely requires CD11/CD18 but Fc gamma RI-mediated ADCC does not. Among subunits of CD11/CD18, appeared to be most involved in lysis of sensitized SRBC.

Activated phagocytes are involved in the pathogenesis of Crohn's disease (CD). To clarify the activation of polymorphonuclear leukocytes (PMN) from CD patients in relationship with the clinical status, we investigated not only the expression of Fc receptor for IgG (huFc gamma R) but also the ability of the PMN to produce free oxygen radicals on stimulation of these receptors by using chemiluminescent techniques. The PMN obtained from the patients with active disease showed an enhanced chemiluminescence (CL) in response to huFc gamma RI stimulation, and an increased expression of huFc gamma RI. Moreover, PMN with huFc gamma RI were recognized in the colonic inflammatory lesions. After a successful treatment, however, we could hardly detect both the CL production and the expression of huFc gamma RI. Thus, it is suggested that the measurement of CL production through huFc gamma RI and the evaluation of the expression of huFc gamma RI are useful to evaluate the clinical status of the CD patients in a more accurate manner. The involvement of huFc gamma RI positive PMN in tissue destruction has been discussed.

Leukocyte adhesion deficiency (LAD) is a hereditary disease characterized by defective expression of leukocyte adhesion glycoproteins; lymphocyte function-associated Ag-1 (CD11a/CD18), CR3 (CD11b/CD18) and p150,95 (CD11c/CD18). Granulocytes, monocytes, and lymphocytes of patients with LAD show profoundly defective in vivo and in vitro adherence-dependent immune functions. We investigated the expression of FcR for IgG on polymorphonuclear cells (PMN) and monocytes from patients with LAD, and their luminol- and lucigenin-enhanced chemiluminescence production in response to SRBC sensitized with murine (m) IgG2a and IgG2b. Unstimulated patient PMN showed an enhanced chemiluminescence in response to mIgG2a-SRBC and an increased phagocytosis of mIgG2a-SRBC. The up-regulated functions were inhibited by monomeric human IgG in a dose-dependent manner, which was attributed to an increase in expression of FcRI on patient PMN, as shown by flow cytometry using monoclonal antibody, 32.2, specific for human FcRI. In contrast, neither the expression of FcR on the monocytes of LAD patients nor their FcR-mediated functions were different from those of controls.

Anti-idiotypic antibodies (anti-Id) against anti-HBs were found in the sera of patients with chronic hepatitis type B. Anti-idiotypic antibodies were detected by an enzyme-linked immunosorbent assay using horseradish peroxidase conjugated mouse monoclonal anti-HBs. Ten of 72 HBsAg positive sera contained anti-Id (13.9%). The prevalence of anti-Id did not appear to correlate with HBeAg/anti-HBe system. However, HB virus specific DNA polymerase activity was significantly higher in anti-Id positive sera. In the sera obtained from the patients treated with predonisolone before, anti-Id positive rate was higher than that in the patients without a history of predonisolone therapy. These results suggest that anti-Id may be related to the immunoregulatory mechanism of HB virus replication.