Cellular and growth factor requirements for the direct and indirect oxidative induction of interleukin 2 responsiveness in human thymocytes.

Human thymocytes were separated by peanut agglutinin (PNA) into PNA+ and PNA- cell fractions, and directly oxidized by the combined action of the enzymes neuraminidase and galactose oxidase (NAGO). Such treatment resulted in the induction of interleukin 2 (IL-2) responsiveness in PNA- cells but not in PNA+ cells. The molecular basis for the poor IL-2 responsiveness of PNA+ cells resides in their inability to express sufficient amounts of IL-2 receptors in response to NAGO treatment. Irradiated oxidized PNA+ or PNA- cells are able to transmit an oxidative mitogenic signal to autologous native PNA- cells but not to PNA+ cells. Depletion of plastic adherent cells from the PNA+ subpopulation totally abolished its high potency for the indirect signal transduction, whereas accessory cell depleted PNA- cells were affected to a lesser extent. Nonspecific esterase staining indicated that human thymic macrophages/monocytes are PNA+ cells. In spite of their small number (less than 0.5% of the total thymus cells) they appear to be very active in the indirect oxidative signal transmission. Unlike the indirect system, direct oxidative mitogenesis is independent of accessory cells. Attempts to detect NAGO-dependent IL-2 receptor inducing soluble factors were fruitless and there is a strict need for cell-cell interaction for the indirect transmission of the oxidative mitogenic signal.