Adoptive transfer of nontransgenic mesenteric lymph node cells induces colitis in athymic HLA-B27 transgenic nude rats

Abstract

SummaryHLA-B27 transgenic (TG) rats develop spontaneous colitis when colonized with intestinal bacteria, whereas athymic nude (rnu/rnu) HLA-B27 TG rats remain disease free. The present study was designed to determine whether or not HLA-B27 expression on T cells is required for development of colitis after transfer of mesenteric lymph node (MLN) cells into rnu/rnu HLA-B27 recipients. Athymic nontransgenic (non-TG) and HLA-B27 TG recipients received MLN cells from either TG or non-TG rnu /+ + + + heterozygous donor rats that contain T cells. HLA-B27 TG rnu/rnu recipients receiving either non-TG or TG MLN cells developed severe colitis and had higher caecal MPO and IL-1β β β β levels, and their MLN cells produced more IFN-γ γ γ γ and less IL-10 after in vitro stimulation with caecal bacterial lysate compared to rnu/rnu non-TG recipients that remained disease free after receiving either TG or non-TG cells. Interestingly, proliferating donor TG T cells were detectable one week after adoptive transfer into rnu/rnu TG recipients but not after transfer into non-TG recipients. T cells from either non-TG or TG donors induce colitis in rnu/ rnu TG but not in non-TG rats, suggesting that activation of effector T cells by other cell types that express HLA-B27 is pivotal for the pathogenesis of colitis in this model.

Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa5

“…16 Although the exact underlying mechanism has not been characterized yet, it has been shown that HLA-B27-expressing innate immune cells have an essential role in determining mucosal immune responses to commensal bacteria in the development of colitis in transgenic rats. 17 Additionally, we have shown in several controlled rat and human studies that dietary calcium improves intestinal resistance against infections with foodborne bacterial pathogens and that it strengthens the mucosal barrier. [18][19][20] It is hypothesized that calcium exerts this protection in part by precipitating irritating bile acids and fatty acids, thereby reducing cytotoxicity of the fecal stream.…”

CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus

“…Even if rnu/rnu TG rats carry the disease-prone B27 transgenic locus, they are protected from disease, whereas the presence of T cells in their heterozygous rnu/ϩ TG littermates coincides with the development of colitis under SPF conditions. 12,13 The critical role of T cells in the induction of intestinal inflammation in this model was further emphasized by the development of colitis in SPF rnu/rnu HLA-B27 TG recipients after T cells had been transplanted, with CD4 ϩ T cells being more efficient than CD8 ϩ T cells in transferring disease. 12 Most studies of HLA-B27 TG rats have been carried out under SPF conditions.…”

Aberrant innate immune responses in TLR-ligand activated HLA-B27 transgenic rat cells

“…23 In contrast, non-TG nude recipients remain disease-free even after transfer of activated TG T cells. 23 Breban et al 24 previously reported that transfer of bone marrow-cells from colitic HLA-B27 TG rats to lethally irradiated disease-resistant non-TG rats or rats with low expression levels of HLA-B27 induced intestinal inflammation, and the disease was related to the generation of donor-derived CD11b/c-expressing cells. Conversely, established disease in TG recipients was reversed 6 -8 weeks after transfer of non-TG bone marrow cells.…”

“…20,21 It has been demonstrated that development of intestinal inflammation in HLA-B27 TG rats is dependent on HLA-B27 expression by cell types, most likely dendritic cells and macrophages, that function as accessory cells for T cell immune responses. Colitis does not occur in nude HLA-B27 TG rats but rapidly develops after T cell reconstitution, 22,23 whether or not the transferred T cells express HLA-B27. 23 In contrast, non-TG nude recipients remain disease-free even after transfer of activated TG T cells.…”

“…Colitis does not occur in nude HLA-B27 TG rats but rapidly develops after T cell reconstitution, 22,23 whether or not the transferred T cells express HLA-B27. 23 In contrast, non-TG nude recipients remain disease-free even after transfer of activated TG T cells. 23 Breban et al 24 previously reported that transfer of bone marrow-cells from colitic HLA-B27 TG rats to lethally irradiated disease-resistant non-TG rats or rats with low expression levels of HLA-B27 induced intestinal inflammation, and the disease was related to the generation of donor-derived CD11b/c-expressing cells.…”