concanavalin-a and Liver-Diseases--Parasitic

Reinfection with Schistosoma mansoni following chemotherapy often results in an ameliorated granulomatous reaction and hence a mild disease. This study examined some of the immunological mechanisms that could be associated with this residual protection. BALB/c mice were infected with either a single dose (group A) of 100 S. mansoni cercariae or with 10 doses of 10 cercariae each (group B) given at 3-day intervals. The mice were treated with praziquantel 8 weeks postinfection and, 2 weeks later, together with another group of naive mice (group C), they were infected with a single dose of 100 cercariae each. All the animals were killed 8 weeks later and schistosome egg antigen (SEA)- and soluble adult worm antigen preparation (SWAP)-induced cytokine recall responses in splenocytes, as well as serum immunoglobulin levels, were quantified and hepatic granuloma sizes measured. Group A animals had higher levels of SEA-induced interferon-gamma (IFN-gamma) but lower levels of interleukin (IL)-5 than groups B and C (P < 0.01). Group B animals had low SEA-induced IFN-gamma levels and elevated IL-5 levels, although these were lower than group C. SEA-induced IL-10 was low in both groups A and B as compared to group C (P < 0.01). SWAP was less effective as an inducer of splenocyte cytokine production than SEA but both SWAP-induced IFN-gamma and IL-5 were detected in groups A and C. SEA- and SWAP-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) titres were not significantly different between the three groups. Granuloma diameters were larger in group C (mean 297 +/- 51.3 microm) as compared to groups A (174 +/- 49 microm, P < 0.01) and B (247.5 +/- 44 microm, P < 0.05). Taken together, these results demonstrate that granuloma size is reduced during a reinfection exposure compared with a primary infection. This reduction is associated with a T helper 1 response in mice exposed to a single large dose of cercariae in the primary infection and with a predominantly T helper 2 response in those infected with multiple small doses.

Topics: Animals; Antibodies, Helminth; Antigens, Helminth; Cells, Cultured; Concanavalin A; Culture Media; Cytokines; Female; Granuloma; Liver Diseases, Parasitic; Mice; Mice, Inbred BALB C; Praziquantel; Recurrence; Schistosoma mansoni; Schistosomiasis mansoni; Spleen; Th1 Cells; Th2 Cells

Schistosomiasis causes pathology in an estimated 200 million individuals. Clinical disease is caused by a complex immunopathologic response to the parasite ova, which are deposited in the host tissues. This immunopathologic response is caused by T lymphocytes which express the high-affinity IL-2 receptor (IL-2R). DAB389IL-2 is a diphtheria toxin-IL-2 fusion toxin protein which functionally inactivates or kills cells which bear the high-affinity IL-2R. DAB389IL-2 has been used in man to suppress IL-2R-dependent immune reactivity. Therefore, we reasoned that DAB389IL-2 might suppress immunopathology in schistosomiasis. In these studies we assessed the in vitro and in vivo effects of DAB389IL-2 on the development of immunopathology in murine schistosomiasis. DAB389IL-2 suppressed IL-2, lectin mitogen (Con A), and soluble Schistosoma mansoni egg antigen-induced lymphocyte proliferation and in vitro granuloma formation. In addition, DA-B389IL-2 suppressed in vitro IL-2R expression. DA-B389IL-2 also suppressed the development of granulomas and collagen deposition in vivo in the livers of infected animals. Therefore, DAB389IL-2 may have potential for the targeted reduction of immunopathology due to schistosomiasis in man.

Topics: Animals; Antigens, Helminth; Cell Division; Concanavalin A; Diphtheria Toxin; Epitopes; Granuloma; Immunosuppressive Agents; Immunotoxins; Interleukin-2; Liver Diseases, Parasitic; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Receptors, Interleukin-2; Recombinant Fusion Proteins; Schistosomiasis mansoni

Highly susceptible mice were infected with Leishmania donovani chagasi and were treated with supernatants, free or encapsulated in liposomes, from concanavalin A-stimulated or unstimulated mouse spleen cell cultures. Treatment consisted of multiple i.v. injections beginning 2 days before to 2 days after infection. Mice treated with lymphokine-rich supernatants encapsulated in liposomes had significantly fewer liver parasites than the control groups, demonstrating in vivo activity of lymphokine against an infectious organism.

Topics: Animals; Concanavalin A; Immunotherapy; Leishmania; Leishmaniasis, Visceral; Liposomes; Liver Diseases, Parasitic; Lymphokines; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Spleen