Characterization of CD4+CD8αα+ and CD4–CD8αα+ intestinal intraepithelial lymphocytes in rats

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Abstract
Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4+CD8αα+ and CD4–CD8αα+ T cells expressing TCR αβ. In the present study, we compared characteristics between CD4+CD8αα+ and CD4–CD8αα+ i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old Lewis rats. Most of the CD4+CD8αα+ i-IEL were of the CD44high phenotype, while CD4–CD8αα+ i-IEL were CD44low. Vβ usage in the CD4–CD8αα+ i-IEL was much diversified, while CD4+CD8αα+ i-IEL showed a skewed Vβ repertoire. The CD4+CD8αα+ i-IEL but not the CD4–CD8αα+ i-IEL proliferated in response to syngeneic spleen cells, which was partially inhibited by addition of anti-MHC class I mAb. The CD4+CD8αα+ i-IEL produced IFN-γ and IL-2 but no IL-4 or transforming growth factor (TGF)-β in response to syngeneic spleen cells, while CD4–CD8αα+ i-IEL produced abundant levels of TGF-β but no IL-2, IFN-γ or IL-4. CD4+CD8αα+ i-IEL proliferated in response to exogenous IL-2 but not to IL-15, while CD4–CD8αα+ i-IEL could respond to IL-15 as well as IL-2. These results suggest that a significant fraction of CD4+CD8αα+ i-IEL belongs to Th1-type T cells capable of responding to self-MHC class I, while CD4–CD8αα+ i-IEL are a unique population with a diversified Vβ repertoire that respond to IL-15 in rats.