Anti-CCL25 monoclonal antibody, clone 90929

The CC chemokine CCL25 (TECK) is selectively expressed in the thymus and small intestine, indicating a potential role in T lymphocyte development. In the present study we examined the role of CCL25 in the generation of the small-intestinal CD8alphaalpha(+)CD3(+) intraepithelial lymphocyte (IEL) compartment. CCL25 mRNA expression in the murine small intestine increased at three weeks of age and corresponded with the appearance of CD8aa+CD3+ lymphocytes in the small-intestinal epithelium. Administration of monoclonal neutralizing anti-CCL25 antibody to two-week-old mice led to a similar to50% reduction in the total number of CD8alphaalpha(+)TCRgammadelta(+) and CD8alphaalpha(+)TCRalphabeta(+) IEL at four weeks of age. Freshly isolated murine CD8alphaalpha(+)CD3(+) IEL migrated in response to CCL25 and expressed the CCL25 receptor, CCR9. Analysis of CCR9 expression on putative IEL precursor populations demonstrated the presence of both CCR9(-) and CCR9(+) cells and indicated that up-regulation of this receptor occurred during IEL precursor differentiation. Finally, data from wild-type and RAG(-/-) mice suggested that the reduction in CD8alphaalpha(+)CD3(+) IEL in anti-CCL25 antibody treated mice resulted primarily from defective maintenance and/or development of IEL precursors rather than a direct effect on mature CD8alphaalpha(+)CD3(+) IEL.

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3 x 10(8) cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer's patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer's patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections.