Genetic control of schistosome infections by the SM1 locus of the 5q31-q33 region 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 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.
Rodrigues
V
V
Laboratorio de Imunologia, Faculdade de Medicina do Triangulo Mineiro, 30, Frei Paulino, 38025-160, Uberaba, MG, Brazil.
Piper
K
K
Couissinier-Paris
P
P
Bacelar
O
O
Dessein
H
H
Dessein
A J
AJ
D000293:Adolescent; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002648:Child; D002895:Chromosomes, Human, Pair 5; D020022:Genetic Predisposition to Disease / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000235:genetics* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D015848:Interleukin-5; D015847:Interleukin-4