Defective killer cell activity in patients with chronic active Epstein-Barr virus infection.

Natural killer (NK) cell activity, lymphokine activated killer (LAK) activity and Epstein-Barr virus specific cytotoxic T lymphocyte (EBV-CTL) activity were examined in 10 children with chronic active EB-virus infection and an adult with persistently positive early antigen-antibody to EB-virus. NK cell activity against erythroleukemia cell line K-562 was significantly (p less than 0.005) lower in the patients (22.3 +/- 8.5%, mean +/- SD) than in normal controls (40.4 +/- 15.9%). Spontaneous cytotoxicity against an EB-virus transformed autologous lymphoblastoid cell line was 15.0 +/- 7.6% in the patients, and was comparable to spontaneous cytotoxicity activity in normal controls (11.7 +/- 4.3%). LAK activity against Raji cells was significantly (p less than 0.02) lower in the patients (14.6 +/- 11.4%) than in normal controls (29.2 +/- 15.9%). EBV-CTL activity against an EB-virus transformed autologous lymphoblastoid cell line was significantly (p less than 0.005) lower in the patients (11.8 +/- 5.5%) than in seropositive normal controls (33.7 +/- 14.7%). No regression of the lymphoblastoid cell line was observed when EBV-CTL activity of the patients was tested by regression assay. It is conceivable that defects in both EB-virus specific and nonspecific killer cell activities play important roles in the pathogenetic abnormalities which allow EB-virus infection to progress to a chronic active state.</p

Elevated IgA antibodies to Epstein-Barr virus in children with chronic active Epstein-Barr virus infection.

Anti-Epstein-Barr virus (EBV) antibodies were tested in 11 children with chronic active EBV infection. Anti-virus capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:10,240. Anti-VCA-IgM antibody was consistently positive in 5 of the 11 patients; anti-VCA-IgA antibody was consistently positive in 6 of the 10 patients; anti-early antigen (EA)-IgG antibody was consistently positive in 10 of the 11 patients and anti-EA-IgA antibody was consistently positive in 4 out of the 7 patients. Anti-EBV nuclear antigen (EBNA) antibody was not detected in two patients. Consistently positive anti-VCA-IgA- and anti-EA-IgA- antibody may be a characteristic feature of abnormal antibody responses in severe chronic active EBV-infection in childhood.</p

Hyperreactivity of lymphocytes to streptolysin O and lack of plasma inhibitory factor (s) in patients with mucocutaneous lymphnode syndrome.

Lymphocyte activation by streptolysin O (SLO) and factors in the plasma which inhibit the response to SLO were examined in 19 patients with mucocutaneous lymphnode syndrome (MCLS), 54 age-matched (6 months-6 years) normal children, 41 normal children older than 6 years and 10 normal adults. In normal children younger than 6 years, the response to SLO was weak and in many cases no response was seen. On the other hand, in the patients with MCLS, the response of lymphocytes to SLO was high and comparable to the response in adults and children older than 6 years. The DNA synthesis of lymphocytes stimulated by SLO was inhibited almost completely by autologous or allogeneic plasma of many of the normal children and adults. The plasma of patients with MCLS did not inhibit, but rather enhanced the response to SLO. These results suggest that the increased response of lymphocytes to SLO and the lack of plasma inhibitory factors in patients with MCLS may be due to the immune response to the pathogen of MCLS, as yet undiscovered.</p

Cell-mediated cytotoxicity-supporting activity of various human gammaglobulin preparations.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.</p