Vaccine 19 (2001) 1218 – 1224 The role of IL-10 and IgG1 in the protection and granulomatous response in Schistosoma mansoni P24-immunized mice Claudia Soares Zouain a , Shauma Gustavson a , Se ´rgio Costa Oliveira a , Vasco Azevedo b , Jose ´ Bento Alves c , Alfredo Miranda Goes a, * a Departamento de Bioquı ´mica e Imunologia, Instituto de Cie ˆncias Biolo ´gicas, Uniersidade Federal de Minas Gerais, Caixa Postal 486, A. Antonio Carlos 6627, CEP 30161 -970 Belo Horizonte, MG, Brazil b Departamento de Biologia Geral, Instituto de Cie ˆncias Biolo ´gicas, Uniersidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil c Departamento de Morfologia, Instituto de Cie ˆncias Biolo ´gicas, Uniersidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Received 16 December 1999; received in revised form 18 July 2000; accepted 1 August 2000 Abstract Previous work by our laboratory identified a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, designated PIII, able to elicit significant in vitro cell proliferation, and lower in vitro and in vivo granuloma formation. In the present work, we investigated some biological activities of P24, an antigenic component of PIII. Immunization of mice with this antigen induced a significant protection degree against challenge infection and significant decrease in the hepatic granuloma formation. Pre-incubation of spleen cells from P24-immunized mice with S. mansoni antigens induced a significant increase of interleukin (IL)-10 levels, but not interferon-, in the cell supernatants. In addition, mice immunized with different S. mansoni antigens and P24 displayed indistinguishable levels of IgG2a in response to anti-S. mansoni antigens, while IgG1 levels were significantly increased. Collectively, our results indicate that P24 might mediate protective anti-parasite immunity and downregu- late granulomatous hypersensitivity to S. mansoni eggs in part by its ability to induce a higher production of IgG1 and IL-10. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Interleukin-10; IgG1; Granuloma; Regulation; Schistosomiasis www.elsevier.com/locate/vaccine 1. Introduction The granulomatous inflammation in infection with Schistosoma mansoni is dependent on schistosome eggs (SEA)-sensitized CD4 + T-helper (Th) cells, and com- prise multiple pathways involving the activation and recruitment of different cell populations and the pro- duction of different cytokines [1–3]. One of the features of schistosomiasis immunobiology is the gradual and spontaneous reduction in the size of granulomatous inflammation around the continuously incoming eggs. This phenomenon, termed immunomodulation [4], has been the subject of numerous studies showing the par- ticipation of cellular as well as subcellular mechanisms in regulation of granulomatous process [5 – 7]. There- fore, the identification of S. mansoni antigens and an assessment of their role in host – parasite interaction, notably in the prevention or decrease in granuloma size by immunization procedure, are essential for the devel- opment of an anti-schistosome vaccine [8]. The future progress in this field depends on understanding the complex immunoregulatory events that modulate the evolution of granulomatous hypersensitivity to S. man - soni eggs and the basis of protective immunity in man [9]. Various experimental approaches have been carried out to identify S. mansoni antigens that elicit T-cell proliferation and granuloma formation, including para- site antigens purified by conventional purification tech- niques [10–13], by affinity chromatography with monoclonal antibodies [14–18] or by recombinant DNA technology [19,20]. Conflicting results were re- ported by different laboratories, notably with respect to the type of antigens that yield the highest levels of resistance [21]. Our laboratory has produced PIII, an * Corresponding author. Tel.: +55-31-4992639; fax: +55-31- 4415963. E-mail address: goes@mono.icb.ufmg.br (A.M. Goes). 0264-410X/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(00)00265-6