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

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 CD44(high) phenotype, while CD4^-CD8αα⁺ i-IEL were CD44(low). V(β) usage in the CD4^-CD8αα⁺ i-IEL was much diversified, while CD4⁺CD8αα⁺ i-IEL showed a skewed V(β) 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 T(h)1-type T cells capable of responding to self-MHC class I, while CD4^-CD8αα⁺ i-IEL are a unique population with a diversified V(β) repertoire that respond to IL-15 in rats.