Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit

Abstract

Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly‐1 T cell. It can be separated from Ly‐1 helper cells by three criteria other than function: its generation is dependent on Ly‐2⁺ cells, it is I‐J⁺, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly‐2⁺ cells for generation and neither express determinants that our anti‐I‐J antisera recognize nor stick to V. villosa. The mechanism by which these Ly‐1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly‐2 suppressor cells and in vivo immunized Ly‐1.1‐congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly‐1.2 contrasuppressor cells and the Ly‐2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly‐1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly‐1 helper cells by the Ly‐2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.