Genetic control of schistosome infections by the SM1 locus of the 5q31-q33region is linked to differentiation of type 2 helper T lymphocytes

Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33, This genetic region encodes cytokine s which regulate the development of helper T lymphocytes, In the present wo rk, a clonal analysis of CD4(+) T lymphocytes of homozygous resistant and h omozygous susceptible subjects was undertaken to evaluate whether SM1 contr ols helper T-cell differentiation. Of 121 CD4(+) T-cell clones (TCC) from t hree susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens, Parasite-specific TCC derived from suscep tible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 acid -5 than TCC from resistant subjects (25 RTCC). Clones from both patient gr oups produced, however, the same amount of gamma interferon. Parasite-speci fic 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, i ndicate that the SM1 locus controls the differentiation of Th2 lymphocytes.