[in Japanese]

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Studies on recombinant BCG (rBCG) which my group carried out so far were reviewed. Recombinant BCG which secreted a antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. Thus, rBCG secreting merozoite surface protein I (MSPI) of Plasmodium yoelii efficiently protected the infection more than recombinant MSP 1 mixed with artificial adjuvant RAS or IFA did. rBCG which secreted excess amounts of antigen 85 complex A inhibited the multiplication of M. leprae in the footpads of mice. rBCG which secreted a antigen-fused IL-2 stimulated peritoneal exudate cells of mice resulting in enhancing killing a bladder cancer cell line in vitro.

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Cell-mediated immunity, which is activated through the macrophage-cytokine-CD4 helper T cell axis, plays a key role in host defense against mycobacterial infection. In the process, protection in the host is a local event focused on granulomatous lesions that may lead to tissue damage including caseous necrosis, cavity formation, fibrosis, and consequently respiratory failure and marked deformity. The immune response to tuberculosis is a double-edged sword that may contribute to both clearance of infection and tissue damage. In experimental mouse models, immune-based intervention by interleukin (IL) 12 replacement therapy showed antimycobacterial activity in established infection but simultaneously induced both local and systemic toxicities, such as augmentation of granulomatous inflammation and damage to muscles, liver, and blood. Intermittent combination therapy including antimicrobial chemotherapy (rifamycins) and cytokine (IL-12) immune therapy resulted in maximal defense and minimal inflammation without toxicities. Although observations in mice cannot necessarily be extrapolated directly to humans, there has been a continuing hope that immunebased intervention and combination therapy, available in potentially unlimited quantities by biotechnology, albeit at considerable expense, would have a major impact on treatment of infectious diseases caused by drugresistant microorganisms. In addition, the understanding of host defense mechanisms facilitates development of new vaccines for mycobacterial diseases.

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Facultative intracellular bacteria are resistant to the killing mechanism inside macrophages by virtue of various escape mechanisms. Activation of macrophages by cytokines is the key event to overcome of bacterial escape in macrophages of the infected host. Generation of TH1 type of antigen-specific T cell is the essentially required for the macrophage activation. This short review summarizes the escape mechanism of activated macrophages and the mechanisms involved in the generation of TH1 cells.

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HIV-1 infection is a major cause of worldwide epidemic of tuberculosis. HIV-1 infection, even in its early stages, markedly reduces effective immune response to M. tuberculosis. In Japan, the cumulative number of the patients reported is 131 by the end of 1999 with 10 to 20 annual new cases. Most of Japanese cases are advanced AIDS patients with low CD4 number less than 100/ml. The peak of Japanese patient age is 40 to 60 years old, whereas that of foreigners is 20-30 years old, suggesting that most Japanese cases are recurrent tuberculosis. There is increasing clinical evidence that coinfection with M. tuberculosis accelerates progression of AIDS. We found that, in vivo, HIV-1 load and mutation increase in involved lung segments in patients with pulmonary tuberculosis. The promotion of HIV-1 production is not only due to activated translocation of a nuclear factor, NF-kB, but also due to reduced inhibitory factor, C/EBPb 16 kD which binds to HIV LTR and represses the transcription of HIV-1..

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Here, we report the clinico-pathological findings of Buruli ulcer. The patients were 2 females, 9 and 23 years of age and one male, 47 years of age from the Ashanti Country of Ghana. Clinically, cutaneous lesions were classified as nodular, ulcero-nodular and ulcerative. Histopathologically, lesions involved cutaneous and subcutaneous tissue, which showed lympho-epithelioid cell proliferation and panniculitis with characteristic fat necrotic changes. Vascular inflammation, with the nerve tissue involvement, are prominent features on the chronological spectrum of the 3 cases. In all but the early case, Mycobacterium ulcerans could be visualized from the mid dermal area to the subcutis by Fite-Faraco and Harada stain. The ulcerated lesions were also immunoreactive to phenolic glycolipid-1(PGL-1). These findings suggest Mycobacterium ulcerans infection with lesions of different ages. Further, we also show the need to identify distinct caracteristics for differential diagnosis with lesions caused by other mycobacteria.

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Pure neuritic leprosy (PN leprosy) is a type of leprosy with nerve involvement, but without obvious skin lesions. It is not uncommon in the south of Bangladesh, ¹⁾ but its nature is less recognized than that in other types of leprosy. Male is dominant on its occurrence with higher disability grading. The histopathological study shows that the entire spectrum can be observed in nerves of PN leprosy.²⁾³⁾ There was no relation among clinical parameters, such as the number and distribution of affected nerves, the immune response and its histopathology.³⁾ Therefore the treatment of PN leprosy is not well-established at field level. Out of 1, 741 newly detected cases by Dhanjuri Leprosy Project-Khulna Branch (PIME Sisters) in Khulna, the south of Bangladesh from 1994 to 1998, 141, or 8.10 % were diagnosed as PN leprosy. 6 cases out of 1, 741, or 0.34% were canceled afterwards because of wrong diagnosis, of which one misdiagnosed as PN leprosy. Three cases out of 140 of primary neuritic leprosy proved to have obvious skin lesions some time after their treatment started. The details of the three cases are described in this paper.

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