Clin. exp. Immunol. (1978) 34, 46-51.
The role of macrophages in the lymphoproliferative response to mycobacterium leprae in vitro H. HIRSCHBERG* Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia and Tissue Typing Laboratory, National Hospital of Norway, University Hospital, Oslo, Norway (Received 2 May 1978)
SUMMARY
Peripheral blood lymphocytes from patients suffering from lepromatous leprosy do not normally react in vitro to stimulation by Mycobacterium leprae antigens. In contrast, we found that T cells from non-responding patients in combination with macrophages from responding patients or healthy contacts did respond well to M. leprae. Conversely, T cells from responding patients or healthy contacts in combinations with macrophages from non-responding patients failed to respond. It seems, therefore, that the lack of response normally observed in in vitro tests using cells from lepromatous leprosy patients is due to a failure of their macrophages to present M. leprae antigens in an immunogenic form. INTRODUCTION The activation of sensitized T lymphocytes by many antigens and mitogens assessed by lymphocyte proliferation in vitro involves co-operation between lymphocytes and macrophages (van Furth, 1975). This has also been shown for human cells in experiments involving a variety of antigens (Cline & Swett, 1968; Hersh & Harris, 1968; Berlinger, Lopez & Good, 1976). Recently evidence has also been presented suggesting that the immune response (Ir genes) are expressed by macrophages and that animals that are poor responders to a particular antigen are so due to the fact that their macrophages lack the ability of processing or presenting antigen to T cells (Shevach & Rosenthal, 1973; Schwartz et al., 1976; Rosenthal, Barcinski & Blake, 1977). Macrophages also function as host cells for obligate intracellular bacteria and parasites such as Mycobacterium tuberculosis, Brucella, Leishmania and M. leprae. The immunity towards infection by these intracellular bacteria and parasites would, in the final analysis, depend on T cell-macrophage interactions (Godal, Rees & Lamvik, 1971). In the low resistant diffuse form of leprosy, lepromatous leprosy (LL), vast numbers of bacilli are present in the tissues, in particular in the tissue macrophages, and little or no cell-mediated immunity against M. leprae is apparent, while in the high resistant form of the disease, tuberculoid leprosy (TT), and in healthy contacts, pronounced cell-mediated immunity exists (Ridley & Jopling, 1966; Godal, Lofgren & Megassi, 1972). The disease spectrum between these polar forms is paralleled by a spectrum of responses of peripheral blood lymphocytes to M. leprae as antigen in vitro with lymphocytes from LL patients showing a complete lack of responsiveness (Godal et a!., 1971; Godal et al., 1974). This cellular tolerance towards M. leprae is thought to play an important role in the pathogenesis of the disease. A similar spectrum for human tuberculosis has also been described (Lenzini, Rottoli & Rottoli, 1977). The ability of macrophages from responding leprosy patients or normal healthy contacts to restore the proliferative response of T cells from non-responding leprosy patients towards M. leprae has been * Present address and correspondence: Dr H. Hirschberg, Tissue Typing laboratory, National Hospital of Norway, University Hospital, Oslo 1, Norway. 0099-9104/78/0100-0046$02.00 (C1978 Blackwell Scientific Publications
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The role of macrophages in the lymphoproliferative response to mycobacterium leprae in vitro H. HIRSCHBERG* Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia and Tissue Typing Laboratory, National Hospital of Norway, University Hospital, Oslo, Norway (Received 2 May 1978)
SUMMARY
Peripheral blood lymphocytes from patients suffering from lepromatous leprosy do not normally react in vitro to stimulation by Mycobacterium leprae antigens. In contrast, we found that T cells from non-responding patients in combination with macrophages from responding patients or healthy contacts did respond well to M. leprae. Conversely, T cells from responding patients or healthy contacts in combinations with macrophages from non-responding patients failed to respond. It seems, therefore, that the lack of response normally observed in in vitro tests using cells from lepromatous leprosy patients is due to a failure of their macrophages to present M. leprae antigens in an immunogenic form. INTRODUCTION The activation of sensitized T lymphocytes by many antigens and mitogens assessed by lymphocyte proliferation in vitro involves co-operation between lymphocytes and macrophages (van Furth, 1975). This has also been shown for human cells in experiments involving a variety of antigens (Cline & Swett, 1968; Hersh & Harris, 1968; Berlinger, Lopez & Good, 1976). Recently evidence has also been presented suggesting that the immune response (Ir genes) are expressed by macrophages and that animals that are poor responders to a particular antigen are so due to the fact that their macrophages lack the ability of processing or presenting antigen to T cells (Shevach & Rosenthal, 1973; Schwartz et al., 1976; Rosenthal, Barcinski & Blake, 1977). Macrophages also function as host cells for obligate intracellular bacteria and parasites such as Mycobacterium tuberculosis, Brucella, Leishmania and M. leprae. The immunity towards infection by these intracellular bacteria and parasites would, in the final analysis, depend on T cell-macrophage interactions (Godal, Rees & Lamvik, 1971). In the low resistant diffuse form of leprosy, lepromatous leprosy (LL), vast numbers of bacilli are present in the tissues, in particular in the tissue macrophages, and little or no cell-mediated immunity against M. leprae is apparent, while in the high resistant form of the disease, tuberculoid leprosy (TT), and in healthy contacts, pronounced cell-mediated immunity exists (Ridley & Jopling, 1966; Godal, Lofgren & Megassi, 1972). The disease spectrum between these polar forms is paralleled by a spectrum of responses of peripheral blood lymphocytes to M. leprae as antigen in vitro with lymphocytes from LL patients showing a complete lack of responsiveness (Godal et a!., 1971; Godal et al., 1974). This cellular tolerance towards M. leprae is thought to play an important role in the pathogenesis of the disease. A similar spectrum for human tuberculosis has also been described (Lenzini, Rottoli & Rottoli, 1977). The ability of macrophages from responding leprosy patients or normal healthy contacts to restore the proliferative response of T cells from non-responding leprosy patients towards M. leprae has been * Present address and correspondence: Dr H. Hirschberg, Tissue Typing laboratory, National Hospital of Norway, University Hospital, Oslo 1, Norway. 0099-9104/78/0100-0046$02.00 (C1978 Blackwell Scientific Publications
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