Abstract
We have previously demonstrated in a rat model of immunodeficiency, an increase in the number of γδ T cells in the gut lamina propria and in the number of CD8αα+, CD25+, γδ+ subpopulations of intestinal intraepithelial lymphocytes (iIEL). The increased percentage of CD8αα+ iIEL that express CD25 indicates inflammation. The present study confirms the existence of an inflammatory process in the immunodeficient animals (R21) that is not detectable at the histological level but is characterized by an increase of the pro-inflammatory cytokines TNF-α and IFN-γ. We have shown a direct relationship between TNF receptor II (TNF-RII) expression and the higher levels of the γδ+ iIEL expressing TNF-α (TCRγδ+/TNF-α+ cells) that could be indicating a differential T cell reactivity. The effects of the increased expression of inflammatory cytokines such as TNF-α and INF-γ seem to be down regulated by the high levels of antigen specific TGF-β expression, which, we believe, is antigen specific and appears to maintain oral tolerance. Finally, in malnourished animals NF-κB remains principally in the cytosol and is unable to translocate to the nucleus, indicating the existence of alterations in the metabolic pathways leading to nuclear factor κB translocation from the cytoplasm to the nucleus. The therapeutic action of the immunomodulator TmB was demonstrated by its capacity to return all the cytokines studied to control levels. Moreover, its effects allowed the transcription factor NF-κB to translocate to the nucleus from the cytosol.