Immune suppression in vivo with antigen-modified syngeneic cells. II. T cell-mediated nonresponsiveness to fowl gamma-globulin.

Intravenous administration of syngeneic spleen cells coupled with the palmitoyl derivative of fowl gammma-globulin (p-F gamma G) results in a profound state of F gamma G-specific tolerance in C57BL/6 mice. Administration of p-F gamma G coupled syngeneic cells specifically reduces both the primary and secondary hapten and carrier-specific PFC responses to TNP-F gamma G. Since the haptenic response is affected, the tolerance functions at the level of the F gamma G-specific helper T cell. As few as 10(3) p-F gamma G spleen cells carrying only 1 ng of p-F gamma G can induce tolerance. At least a 2-day-induction period is required. This nonresponsiveness is long lived, lasting over 120 days. Spleen cells from tolerized mice can transfer suppression to normal syngeneic recipients. Treatment of tolerant spleens with anti-Thy 1.2 antiserum + C eliminates the suppressor cell activity. In addition, thymocytes and purified splenic T cells from tolerized mice can transfer suppression to normal recipients. Thus, at least a component of this nonresponsiveness is mediated by suppressor T cells. The requirement of antigen association with cell membrane components and the general applicability of this method of inducing T cell nonresponsiveness are discussed.