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This study used selected lambs that varied in their resistance to the gastrointestinal parasite  Teladorsagia circumcincta . Infection over 12 weeks identified susceptible (high adult worm count, AWC; high fecal egg count, FEC; low body weight, BW; low IgA) and resistant sheep (no/low AWC and FEC, high BW and high IgA). Resistance is mediated largely by a Th2 response and IgA and IgE antibodies, and is a heritable characteristic. The polarization of T cells and the development of appropriate immune responses is controlled by the master regulators, T-bet ( TBX21 ), GATA-3 ( GATA3 ), RORγt ( RORC2 ) and RORα ( RORA ); and several inflammatory diseases of humans and mice are associated with allelic or transcript variants of these transcription factors. This study tested the hypothesis that resistance of sheep to  T .  circumcincta  is associated with variations in the structure, sequence or expression levels of individual master regulator transcripts. We have identified and sequenced one variant of sheep  TBX21 , two variants of  GATA3  and  RORC2  and five variants of  RORA  from lymph node mRNA. Relative RT-qPCR analysis showed that  TBX21 ,  GATA3  and  RORC2  were not significantly differentially-expressed between the nine most resistant (AWC, 0; FEC, 0) and the nine most susceptible sheep (AWC, mean 6078; FEC, mean 350). Absolute RT-qPCR on all 45 animals identified  RORVv5  as being significantly differentially-expressed (p = 0.038) between resistant, intermediate and susceptible groups;  RORCv2  was not differentially-expressed (p = 0.77). Spearman’s rank analysis showed that  RORAv5  transcript copy number was significantly negatively correlated with parameters of susceptibility, AWC and FEC; and was positively correlated with BW.  RORCv2  was not correlated with AWC, FEC or BW but was significantly negatively correlated with IgA antibody levels. This study identifies the full length  RORA  variant ( RORAv5 ) as important in controlling the protective immune response to  T .  circumcincta  infection in sheep.

Variations in T Cell Transcription Factor Sequence and Expression Associated with Resistance to the Sheep Nematode Teladorsagia circumcincta