Abstract

Genetic Control of Schistosome Infections by the SM1 Locus of the 5q31-q33 Region Is Linked to Differentiation of Type 2 Helper T Lymphocytes Virmondes Rodrigues Jr. 1 , 2 , Karen Piper 2 , Patricia Couissinier-Paris 2 , Olivia Bacelar 2 , Hélia Dessein 2 and Alain J. Dessein 2 , * Laboratorio de Imunologia, Faculdade de Medicina do Triangulo Mineiro, 30, Frei Paulino, 38025-160, Uberaba, MG, Brazil, 1 and INSERM U399, Immunology and Genetic of Parasitic Diseases, Faculté de Médecine de Marseille, Université de la Méditerranée, Marseille, France 2 ABSTRACT Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33. This genetic region encodes cytokines which regulate the development of helper T lymphocytes. In the present work, a clonal analysis of CD4 + T lymphocytes of homozygous resistant and homozygous susceptible subjects was undertaken to evaluate whether SM1 controls helper T-cell differentiation. Of 121 CD4 + T-cell clones (TCC) from three susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens. Parasite-specific TCC derived from susceptible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 and -5 than TCC from resistant subjects (25 RTCC). Clones from both patient groups produced, however, the same amount of gamma interferon. Parasite-specific STCC were type 1 helper (Th1) or Th0/1, whereas RTCC were either Th2 or Th0/2. These results, together with the localization of SM1 in 5q31-q33, indicate that the SM1 locus controls the differentiation of Th2 lymphocytes.