Expression of The Ectoenzyme RT6 is Not Restricted to Resting Peripheral T Cells and is Differently Regulated in Normal Peripheral T Cells, Intestinal IEL, and NK Cells

Abstract

The RT6 alloantigenic system of the rat has originally been defined on T lymphocytes of the peripheral lymphatic organs and has been considered to be selectively expressed on mature peripheral T cells. Studying NK cells and intestinal intraepithelial lymphocytes (IEL), we have now found that both cell types also express RT6 and that the expression patterns found for IEL and NK cells were markedly different from each other and also from the expression pattern previously described for T cells of the peripheral lymphatic organs. In lymph nodes, spleen, and blood both RT6 and RT6⁺ T cells have been found and the density of RT6 expression on the positive cells has been shown to vary over a broad range. In contrast more than 98% of intestinal IEL stained for RT6 and the RT6 density was about tenfold higher than on strongly positive T cells of the peripheral lymphatic organs. Furthermore, the same high RT6 density was also found on IEL of athymic nude rats although these cells, to a large extent, lacked other T cell markers. This probably indicates that RT6 expression is an early event in the maturation of intestinal IEL which can occur already before the expression of T cell-specific membrane molecules. The conclusion that the expression of RT6 may be differently regulated in IEL and other T cell populations was further substantiated by the observation that RT6 was also present on IEL of diabetes-prone BB rats which are known to lack RT6 positive T cells in peripheral lymphatic organs. For NK cells still another pattern of RT6 expression was found. Unlike peripheral T cells and IEL, only a small subset of NK cells in blood and spleen expressed RT6. The percentage of RT6 positive cells was increased by in vitro stimulation of isolated NK cells with high concentrations of recombinant rat IL-2 indicating that RT6 expression may be associated with an activated state in NK cells. Taken together, these findings demonstrate that the expression of RT6 is not restricted to T cells and is differently regulated in normal peripheral T cells, intestinal IEL, and NK cells. Since it has recently been demonstrated that the RT6 gene contains two functional promoter regions with major structural disparity it is very likely that the distinct patterns of RT6 expression in different cell types reflect the differential use of the two promoters. The development of this complex control of RT6 expression in evolution may have been driven by a beneficial effect resulting from the use of the RT6 molecular function by several different lymphocyte populations.