Effect of T-cell depletion on bacterial multiplication and pattern of nerve damage in M. leprae-infected mice.

Various mechanisms for nerve damage in tuberculoid leprosy have been proposed. A common feature amongst them is the crucial role played by T-cells. Therefore, the present study was designed to determine the role of T-cells in the induction of nerve damage in leprosy using two different protocols for obtaining graded levels of T-cell depletion: (i) Cyclosporine A, for depletion of T-helper cells and (ii) Anti Thy 1.2, for total depletion of T-cells. The findings indicate that the early changes seen in the unmyelinated fibres may not involve T-cells. However, the later stages of nerve damage associated with demyelination are dependent on T-cell responses.

In vitro tests for screening of immuno-modulating mycobacterial strains in leprosy.

There is an urgent need for the development of an in vitro assay for the initial screening of a large number of organisms from which potential candidates as vaccines can be identified. Our previous studies have demonstrated a crucial defect in the lepromatous macrophage. In this study by monitoring this defective macrophage response we have screened various mycobacteria for their ability to reverse the alterations induced by Mycobacterium leprae. Among the limited Mycobacteria tested Mycobacterium vaccae appears to be the most promising as an immunomodulator. Our results also indicate the need for caution in using the mouse model for this purpose.

An indomethacin sensitive suppressor factor released by macrophages of leprosy patients.

Reduction in Fc receptor expression as assayed by ‘erythrocyte’ rosetting of macrophage cultures from long term treated lepromatous leprosy patients (bactereologically negative) was seen in the presence of viable Mycobacterium leprae. Macrophages with and without intracellular bacilli demonstrated this reduction. On the basis of this observation the conditioned medium of Mycobacterium leprae infected macrophage cultures of lepromatous patients, were tested on macrophages from normal individuals for [3H]-leucine incorporation and antigen specific physical interaction with lymphocytes. Both these parameters showed decreased values as compared to the controls which were not exposed to this conditioned medium. Lymphocyte transformation to Mycobacterium leprae in leucocyte cultures of normal individuals was also reduced in the presence of the conditioned medium from lepromatous patients’ macrophages. The indication that this factor may be a prostaglandin was suggested by the observation that its synthesis was inhibited by indomethacin. Its importance in the non-specific depression in cell-mediated immunity seen in lepromatous patients is discussed.