Marrow donor immunity to herpes simplex virus: association with acute graft-versus-host disease.

The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk of GVHD due to donor HSV antibodies. Of 31 recipients of marrow from donors who were both HSV- and CMV-seropositive, 27 (85%) developed GVHD versus 11 of 22 recipients (50%) of marrow from HSV-seropositive but CMV-seronegative donors (p = 0.008).

An enzyme immunoassay to detect specific antibodies to protein and lipopolysaccharide antigens of Chlamydia trachomatis.

We have developed an enzyme immunoassay to measure antibodies to the proteins and lipopolysaccharide (LPS) of Chlamydia trachomatis. Antibodies to proteins could be differentiated from antibodies to lipopolysaccharide (LPS) by treatment of the antigen with periodate or Triton X-100. Some important parameters of the oxidation by periodate were studied by comparing the response of several monoclonal antibodies. Four types of response could be observed: type I, a reduced response after mild or strong oxidation; type II, a normal response after mild oxidation, but reduced after strong oxidation; type III, not affected; type IV, an increased response after oxidation. Treatment with Triton X-100 had the same effect as mild oxidation and confirmed the response types I, III, and IV. Treatment of antigen with periodate reduced the IgG response measured in sera from patients with evidence of Chlamydia psittaci infection.

Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria.

A test for monkeypox-specific antibodies is described. Monkeypox immune sera can be made type-specific by immunoabsorption with heterotypic poxvirus extracts. Monkeypox-specific antibodies were demonstrated in sera from 9 cynomolgus monkeys (Macaca fascicularis) that had previously been experimentally infected with monkeypox. Monkeypox-specific antibodies were found in 3 wild-caught African monkeys (Cercopithecus spp.) and in 3 human sera collected from Africans in the Ivory Coast and Nigeria 3(1/2)-4 years after they had suffered a pox-like infection. Monkeypox had been recognized in one of the patients by virus isolation, and had been suspected in the others for epidemiological reasons. Vaccinia-specific antibodies were found in 4 human sera collected 6 weeks after smallpox vaccination.The serological results provide the first laboratory evidence of a monkeypox reservoir in wild monkeys.

Indirect immunofluorescence test for detection of IgM antibodies to cytomegalovirus.

A technique for the detection of IgM antibodies to cytomegalovirus (CMV) by immunofluorescence was developed. In order to prevent interference by rheumatoid factor in the sera, IgG was removed by prior immunoabsorption with antiserum to gamma Fc. Sera from 63 patients with a rise in titer of antibody to CMV, indicated by complement fixation, were IgM-positive, but yielded negative results on the Paul-Bunnell-Davidsohn test for infectious mononucleosis. Convalescent-phase serum samples from 20 patients with a seroconversion to herpes simplex virus and from 20 patients with a seroconversion to varicella-zoster virus also had no IgM antibodies to CMV. Sera from six of 10 patients with infectious mononucleosis and two of 100 normal blood donors were positive for IgM antibodies to CMV. In 38 of 63 patients, the diagnosis of CMV infection could be made several weeks earlier by the immunofluorescence test than by the complement-fixation test. IgM antibodies to CMV persisted for more than two months after onset of symptoms of the infection.

Cutaneous responses to smallpox revaccination with calf lymph and the effect of fluorocarbon purification of the vaccine.

For several years the routine smallpox revaccination procedures at a central inoculation unit were arranged to assess the relation between vaccine titre (pock count) and success. Calf lymph batches were applied, diluted and undiluted, over a log titre range of 7.0-9.8. The dose-effect relationship did not appear to fit a linear equation on a log-probit scale, except in the lower part of the titre range. Plotted on this scale, the take rates of nearly all vaccine specimens of the required strength (> 10(8) PFU/ml) were lower than anticipated by linear extrapolation from low titres. Differences between batches were noted. These findings relate to pulp processing without purification. Fluorocarbon extraction of the calf skin harvest resulted in a 4-fold increase of vaccine volume with commensurate virus dilution; it also gave clearly higher take rates than parallel nonpurified vaccine specimens, whether at original strength or at 4-fold dilution.

Large-scale use of freeze-dried smallpox vaccine prepared in primary cultures of rabbit kidney cells.

A lyophilized smallpox vaccine made from infected monolayer cultures of primary rabbit kidney cells was used together with a calf lymph vaccine in a field trial in Lombok, Indonesia, in 1973. About 60 000 children below 15 years of age were vaccinated: some 50 000 with the tissue culture vaccine and about 10 000 with calf lymph vaccine. Similar results were obtained with both vaccines in primary vaccinees and in revaccinees as regards the take rate, pock reactions, and serious secondary reactions.

Acquired immunodeficiency syndrome in Rwanda.

To evaluate acquired immunodeficiency syndrome (AIDS) in central Africa a prospective study was done in Kigali, Rwanda, where Kaposi's sarcoma (KS) is endemic. During a 4 week period, 26 patients (17 males and 9 females) were diagnosed. 16 patients had opportunistic infections, associated with KS in only 2; 1 had multifocal KS alone; and 9 had clinical conditions consistent with prodromes of AIDS. All patients had severe T-cell defects characterised by cutaneous anergy, a striking decrease in the number of helper T cells, and a decreased OKT4:OKT8 ratio (mean 0.27). 21 of the 22 adult patients were living in urban centres and many of them were in the middle to upper income bracket. Most of the men were promiscuous heterosexuals and 43% of the females were prostitutes. No patient had a history of homosexuality, intravenous drug abuse, or transfusion in the previous 5 years. This study suggests that AIDS is present in central Africa as an entity probably unrelated to the well-known endemic African KS. An association of an urban environment, a relatively high income, and heterosexual promiscuity could be a risk factor for AIDS in Africa.

Herpes-virus immunity and acute graft-versus-host disease.

The influence of pretransplant herpes-virus antibodies in 126 marrow-graft recipients and their HLA-identical (A, B, C, DR) sibling donors on the incidence of grades II-IV acute graft-versus-host disease (GVHD) was studied in relation to previously reported risk factors for GVHD. Logistic regression procedures were used to control for confounding factors. Increasing donor age (odds ratio 3.7 per decade; p = 0.02) and donor seronegativity for Epstein-Barr virus (EBV; odds ratio 10.1; p = 0.005) were associated with a high incidence of GVHD. Total rather than selective gastrointestinal decontamination (odds ratio 0.1; p = 0.004), donor seronegativity for herpes simplex virus (HSV; odds ratio 0.1; p = 0.003), and recipient EBV-seronegativity (odds ratio 0.05; p = 0.002) were associated with a low incidence of GVHD. Pretransplant EBV and HSV serology may thus contribute substantially to the estimation of the risk for GVHD.

Effects of herpes virus carrier status on peripheral T lymphocyte subsets.

We studied the effects of herpes virus carrier status on peripheral blood T lymphocyte subsets in 334 healthy individuals. IgG-class antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella-zoster virus (VZV) were used as markers for the carrier status of those viruses. CMV carrier status was associated with significant increases in the numbers of some T cell subsets, whereas the carrier status of EBV, HSV, and VZV had no significant effects. The 159 CMV-seropositive individuals had higher numbers of HNK1+ T cells than did the 175 CMV-seronegative individuals [mean (SD), 292 (196)/microL v 164 (89)/microL, respectively], including the CD4+HNK1+ T cells [38 (48)/microL v 9 (13)/microL, respectively] and the CD8+HNK1+ T cells [166 (146)/microL v 73 (54)/microL, respectively]. Morphological and cytochemical studies showed that the expression of HNK1 by the CD4+ and CD8+ T cells was associated with the occurrence of azurophilic cytoplasmatic granules and a loss of nonspecific esterase activity. The numbers of CD4+HNK1+ and CD8+HNK1+ T cells increased proportionally to the levels of the IgG-class CMV antibody titers. We suggest that the increased numbers of CD4+HNK1+ and CD8+HNK1+ granular T cells in CMV carriers reflect the persistent interaction between CMV and the immune system of its hosts.