Hamsters infected with Leishmania donovani develop a disease similar to human
kala-azar. They present
hypergammaglobulinemia, and their T cells do not respond to parasite
antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) from L. donovani-infected hamsters produce high levels of the inhibitory
cytokine transforming growth factor beta (
TGF-beta). Immunohistochemical studies with an anti-
TGF-beta monoclonal antibody (MAb) showed that this
cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of
TGF-beta are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite
antigen or
lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens of L. donovani-infected hamsters caused profound inhibition of the in vitro
antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial
antigens. Moreover, this inhibition was totally abrogated by the anti-
TGF-beta MAb. These results suggest that the immunosuppression observed in
visceral leishmaniasis is, at least in part, due to the abundant production of
TGF-beta during the course of the
infection.