The discussion about the clinical risk of zoonoses in xenotransplantation has recently culminated in the demand for a moratorium on clinical organ transplantation using pig donors. The basis for this discussion was a recent report showing a possible trans-species transmission of pig endogenous retrovirus (PERV) by in vitro transfer to human cell lines. At present, it remains unclear if this could also happen in vivo or in the setting of xenotransplantation. Potential in vivo transfer of PERV after xenotransplantation was investigated in an experimental pig-to-baboon cell transplantation model. Baboons were immunosuppressed with highdose cyclophosphamide (total 45-150 mg/kg) and transplanted with primary porcine aortic endothelial cells (PAEC). Tissue samples (skin, lymph nodes, lung) and peripheral blood leukocytes of 15 baboons, taken about 12-24 months after transplantation of PAEC, were then analyzed by PCR and showed no PERV infection. PERV expression in PAEC was also analyzed: PERV mRNA and reverse transcriptase in the culture supernatant could be detected. In spite of the release of retroviral particles from cultured PAEC, transplantation of these cells into baboon recipients did not result in virus transmission, not even under heavy immunosuppression.
Campylobacter were detected by PCR in feces of monkeys of different species (clinically healthy, with diarrhea, and dead from acute enteric infections). High prevalence of these bacteria in monkeys was revealed. The incidence of C. jejuni DNA in monkeys with acute enteric infections was higher than in healthy animals (69.6 and 51.3%, respectively). The highest percentage (92.3) of positive results was observed in Macaca mulatta with enteric diseases and in macaque dead of these diseases. The presence of C. jejuni in monkeys with diarrhea and the absence of pathogenic enterobacteria (Shigella, Salmonella, Yersinia) in feces probably attest to etiological relationship of acute enteric infections with Campylobacter.
Fifteen cases of generalized peripheral T-cell non-Hodgkin's lymphoma in baboons were phenotyped immunologically and morphologically. Using the updated Kiel classification the cases included low-grade and high-grade lymphomas and low-grade lymphomas that had transformed into high-grade lymphomas. In the low-grade group there were seven cases of lymphocytic type, partly corresponding to chronic lymphocytic leukaemia of T type and to T-zone lymphoma in man. In addition there were four cases of prolymphocytic-lymphocytic type, which show large nodules ("proliferation centres") and which have no equivalent in the Kiel classification. In four cases there was a progression to an immunoblastic lymphoma and in one case to a large cell anaplastic lymphoma. In addition, three cases of large cell anaplastic lymphoma without a low-grade component were found. Both the immunoblastic lymphomas and the large cell anaplastic lymphomas corresponded well with the same types in the Kiel classification. The cases of large cell anaplastic lymphoma were also CD30 positive. Most of these lymphomas were CD4 positive, but there were rare cases that were either CD8 positive, showed both CD4 and CD8 positivity or had lost both antigens. Antigens associated with cell activation were often revealed. All but one baboon had antibodies in the blood against the retrovirus STLV-1 (simian T-cell leukaemia virus 1), which is very similar to human T-cell leukaemia virus 1 (HTLV-1) in man. Despite this virological resemblance, the morphology of these T-cell lymphomas does not resemble that of the HTLV-1-positive Japanese T-cell lymphomas but is like that of the HTLV-1-negative European cases.
Papio hamadryas baboons in the Sukhumi colony develop enzootic outbreaks of malignant lymphomas with an incidence of about 1.5% per year among adults of the high-risk stock. We investigated the surface phenotypes of cells from normal and lymphomatous animals using antibodies against human lymphocyte antigens. We found that more than 80% of the lymphomas that developed during the last 3 years were characterized histologically to be of the peripheral T cell type. Generally, the lymphomatous cells also expressed high levels of MHC class II DR protein, CD18 (LFA-1 beta chain), and CD45RO. Surprisingly, these cells also expressed on their surface two proteins previously characterized as being relatively B cell-restricted: CD40 and Bgp95. These proteins were never found on the peripheral blood T cells from normal animals. The expression of these two gene products was confirmed by RNA blotting and immunoprecipitation. In most cases, the two B cell-associated proteins were expressed on the predominant T cell subsets; we found both B cell proteins on CD4+, CD8+ as well as on the CD4/8 double-positive cells when these subsets were expressed at high levels. About 90% of these animals are seropositive for Herpesvirus papio and human T cell leukemia virus-1 (HTLV-1) before developing outright lymphomas. In all of the lymphoma samples, HTLV-1 tax DNA sequences were detected by PCR amplification. Whether or not HTLV-1 or the Herpesvirus papio gene products influence the surface expression of CD40 and Bgp95 remains to be determined.
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