Immunobiological studies on experimental visceral leishmaniasis. II. Adherent cell-mediated down-regulation of delayed-type hypersensitivity response and up-regulation of B cell activation

Abstract

Visceral leishmaniasis or kala-azar is characterized by a variety of immunopathological consequences in man. The most remarkable of these are the depression of cell-mediated immunity and polyclonal B cell activation. The consequences observed in man could be induced in a murine model by inoculating the causative agent, Leishmania donovani. The cell-mediated response was studied in this murine model in terms of the delayed-type hypersensitivity (DTH) response toward leishmania antigen in a progressive infection. BALB/b (H-2^b) mice showed progressive enhancement in the DTH response, whereas BALB/c (H-2^d) mice showed strong DTH at the onset which gradually disappeared (defined as DTH-negative phase) and reappeared again at the later stage of infection. Adoptive transfer of enriched populations of splenic T cells from infected BALB/c mice together with parasite antigen into the footpad of syngenic normal recipients produced a dramatic enhancement in the DTH response, except at the onset of the DTH-negative phase. These observations indicate that adherent cells have a role in suppression of the cell-mediated immune response and also that another mechanism operates at the onset of the DTH-negative phase. This DTH-negative phase was not caused by depletion of DTH-mediating cells from the repertoire, but rather by suppression mediated by a subset of T cell evolved in the course of infection. Characterization on the basis of lymphokine production of the T cells mediating the DTH response and of T cells mediating suppression of the DTH response showed them to be of T_h1 and T_h2 type, respectively. Studies also indicated that at the onset and the later stages of infection suppression was mediated by adherent cells, but at the onset of DTH-negative phase, in particular, suppression was mediated by T_h2 cells. Furthermore, experiments also showed that adherent cells from infected mice gained another property, that of driving B cells, in a T cell-dependent manner