Regulation of cell-mediated immunity in lepromatous leprosy

G. KAPLAN, Z. A. COHN
1986 Leprosy Review  
Patients with lepromatous leprosy demonstrate a selective T cell unresponsiveness to M. le prae and fail to mobilize appreciable numbers of T cells--particularly of the T4 (helper) phenotype, into their dermal lesions. In the absence of lymphokine production, cutaneous macrophages serve as permissive hosts for the bacilli and extensive intravacuolar replication takes place. In our studies we wished to examine the factors leading to T cell and monocyte emigration into the skin and the role of
more » ... and the role of interferon-y. For this purpose we generated delayed hypersensitivity reactions in the dermis of control and lepromatous patients and examined the nature and host-parasite interactions of the cells accumulating at these sites. In addition, we have administered recombinant, human interferon-y into the skin of patients with leproma tous leprosy. The nature of these reactions at the local and systemic level will be presented. Immunopathology of leprosy lesions The dermal lesions of lepromatous patients are characterized by the presence of large num bers of heavily infected foamy macrophages and a sparse infiltrate of lymphoid cells. Using monoclonal antibodies specific for human leukocyte antigens we have shown that the vast majority of the T cells found in these lesions were of the Leu2aJOKT8 (suppressor/cytotoxic) subset of T lymphocytes (1). Only few Leu3aJOKT4 (helper) T cells were present, and the T4!T8 ratios were considerably less than unity. As one progressed towards the tuberculoid pole, the number of T cells increased and many of them were of the Leu3aJOKT4 phenotype. This was associated with a reduction in the extent of parasitization of the cutaneous macro phages and a differentiation of these into epithelioid and multinucleated giant cells organized within granulomas (2). The exuberant growth of M. leprae within macrophages of lepromatous lesions stands in striking contrast to the paucibacillary macrophages of tuberculoid leprosy. The permissive nature of the macrophages of the lepromatous lesions together with the selective absence of helper T cells suggested a lack of local Iymphokine production and inadequate macrophage activation. The cellular kinetics of delayed type hypersensitivity reactions in the lesions of le promatous leprosy The lack of accumulation of helper T cells in the lesions of lepromatous leprosy focused our attention on the ability of the dermal milieu of these patients to provide the neccesary condi tions for normal cellular immune responses. We wanted to establish whether T4 cells were inhibited from emigrating into the sites of M. leprae infection and whether they could be re tained and activated to release lymphokines in these lesions. For this purpose , we generated
doi:10.5935/0305-7518.19860072 fatcat:4eg2bh42qfemrfuylqokr6ovri