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

Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4(+)CD8 alpha alpha(+) and CD4(-)CD8 alpha alpha(+) T cells expressing TCR alpha beta. In the present study, we compared characteristics between CD4(+)CD8 alpha alpha(+) and CD4(-)CD8 alpha alpha(+) i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old Lewis rats. Most of the CD4(+)CD8 alpha alpha(+) i-IEL were of the CD44(high) phenotype, while CD4(-)CD8 alpha alpha(+) i-IEL were CD44(low). V-beta usage in the CD4(-)CD8 alpha alpha(+) i-IEL was much diversified, while CD4(+)CD8 alpha alpha(+) i-IEL showed a skewed V-beta repertoire. The CD4(+)CD8 alpha alpha(+) i-IEL but not the CD4(-)CD8 alpha alpha(+) i-IEL proliferated in response to syngeneic spleen cells, which was partially inhibited by addition of anti-MHC class I mAb, The CD4(+)CD8 alpha alpha(+) i-IEL produced IFN-gamma and IL-2 but no IL-4 or transforming growth factor (TGF)-beta in response to syngeneic spleen cells, while CD4(-)CD8 alpha alpha(+) i-IEL produced abundant levels of TGF-beta but no IL-2, IFN-gamma or IL-4. CD4(+)CD8 alpha alpha(+) i-IEL proliferated in response to exogenous IL-2 but not to IL-15, while CD4(-)CD8 alpha alpha(+) i-IEL could respond to IL-15 as well as IL-2. These results suggest that a significant fraction of CD4(+)CD8 alpha alpha(+) i-IEL belongs to T(h)1-type T cells capable of responding to self-MHC class I, while CD4(-)CD8 alpha alpha(+) i-IEL are a unique population with a diversified V-beta repertoire that respond to IL-15 in rats.