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.

Blocking of Mycobacterium leprae adherence to dissociated Schwann cells by anti-mycobacterial antibodies.

The association of Mycobacterium leprae with Schwann cells may represent an early crucial step in M. leprae pathogenesis. Using a dissociated Schwann-cell system and anti-mycobacterial monoclonal and polyclonal antibodies directed against surface and cytoplasmic components, we investigated the nature of M. leprae epitopes that mediate cytadhesion. Antibodies to polysaccharide and lipid components of M. leprae cell wall inhibited cytadhesion, whereas those directed against both surface and cytoplasmic protein epitopes did not show any such effect. No synergistic or antagonistic activity in inhibiting cytadhesion was observed when antibodies were used in combination. Thus, the association of M. leprae with Schwann cells may be mediated collectively by more than one of its lipid/polysaccharide epitopes. Also, a role for humoral immunity in intervention in the initial steps of M. leprae pathogenesis needs to be considered.

Effects of a derivative of serotonin (deoxyfructoserotonin) and other antileprosy drugs on attachment and uptake of Mycobacterium leprae by Schwann cells in vitro.

The association (attachment and/or uptake) of Mycobacterium leprae with cultured Schwann cells was studied at 8 and 72 h in the presence of a new antileprosy compound, deoxyfructoserotonin (DFS), as well as conventional antileprosy drugs such as rifampin (RFP) and 4,4'-diaminodiphenyl sulfone (DDS). DFS significantly inhibited bacterial association with Schwann cells at 8 h. RFP also affected the association of M. leprae but not to the same extent as DFS. A similar inhibition at 8 h was noted when M. leprae but not Schwann cells were pretreated with DFS or RFP for 5 days before infection of cultures, implying that modulation was achieved through some form of drug action on bacteria. DDS had no effect on M. leprae association; however, the combination of DFS and DDS was neither antagonistic nor additive. At 72 h postinfection, when attached but noninternalized bacteria were removed with trypsin-EDTA from Schwann cell cultures containing DFS or RFP, a 50% reduction in the number of bacteria in the drug-treated group was obtained as compared with the numbers in drug-free cultures. This indicated a slow entry of M. leprae into Schwann cells in the presence of these drugs. Collectively, these observations point to differing requirements for late and early association of M. leprae with Schwann cells, besides suggesting a role for DFS and RFP in the prevention and minimization of M. leprae-induced nerve damage in vivo.

M. leprae phagocytosis and its association with membrane changes in macrophages from leprosy patients.

Abnormal phagocytosis of Mycobacterium leprae by macrophages of lepromatous patients was demonstrated under various conditions. The largest proportion of macrophages with an excessive bacterial load belonged to the lepromatous group of patients. Lepromatous macrophages treated with Cytochalasin B, an inhibitor of phagocytosis, exhibited a significantly lower degree of ingestion of heat-killed organisms whereas uptake of 'viable' organisms was not affected to the same extent. Regulation of phagocytosis was studied by noting the rate of phagocytosis of M. leprae after the ingestion of a primary particle viz carbonyl iron. Solely in lepromatous macrophages, phagocytosis of carbonyl iron did not result in a decreased uptake of M. leprae implying aberrant phagocytic activity. Lastly, excessive phagocytosis was always noted in macrophages of familial contacts of leprosy patients who displayed decreased Fc receptor expression after M. leprae ingestion. This is of interest since phagocytosis, like Fc receptor expression, is a membrane dependent event and other membrane associated defects have been recognized by us earlier in lepromatous macrophages.

Mycobacterium leprae-induced alterations in macrophage Fc receptor expression and monocyte-lymphocyte interaction in familial contacts of leprosy patients.

Macrophage Fc receptor expression and monocyte-lymphocyte interaction in the presence of Mycobacterium leprae were examined in familial contacts of leprosy patients. Defective M phi functions similar to those of borderline and lepromatous patients could be observed in approximately 71% of consanguineous contacts and 43% of spouses of index patients. Although the values in the latter group were markedly lower than those of the consanguineous contacts, they tended to be higher than those of normal individuals (20%). These in vitro M phi functions were independent of age, sex, and age at onset of exposure and were only weakly associated with duration of exposure. The outcome of the monocyte-lymphocyte interaction test paralleled to a large extent the in vivo Mitsuda lepromin response. Four contacts with defective M phi functions also showed signs of leprosy. The value of these in vitro tests as markers of 'susceptibility' could therefore prove significant.