TRANSFORMING-GROWTH-FACTOR-BETA AND IMMUNOSUPPRESSION IN EXPERIMENTALVISCERAL LEISHMANIASIS

Hamsters infected with Leishmania donovani develop a disease similar t o human kala-azar. They present hypergammaglobulinemia, and their T ce lls do not respond to parasite antigens. This unresponsiveness has bee n primarily ascribed to defects in antigen-presenting cells (APCs), be cause these cells are unable to stimulate proliferation of parasite-sp ecific T cells from immunized animals. In this study, we show that APC s (adherent spleen cells) from L. donovani-infected hamsters produce h igh levels of the inhibitory cytokine transforming growth factor beta (TGF-beta). Immunohistochemical studies with an anti-TGF-beta monoclon al 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 s pontaneously or after stimulation with parasite antigen or lipopolysac charide. Furthermore, in vivo-infected adherent cells obtained from sp leens of L. donovani-infected hamsters caused profound inhibition of t he in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inh ibition 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 durin g the course of the infection.