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Immune Suppression in Vivo with Antigen-Modified Syngeneic Cells

III. Distinctions Between T Cell Tolerance and T Cell Mediated Suppression¹

From the Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115

Abstract

Intravenous administration of syngeneic spleen cells coupled with the palmitoyl derivative of fowl -globulin (p-FG) results in a profound state of FG carrier-specific tolerance in C57BL/6 mice. This nonresponsiveness can be attributed to two independent mechanisms, i.e., T cell tolerance and T cell suppression. The two phenomena could be distinguished on the basis of kinetics of induction, inducer cell dose requirements, and cyclophosphamide sensitivity. Thus, a 3-day period is required for the induction of T cell tolerance, and 7 days are required to induce immune suppression. Furthermore, at least 10⁶ p-FG-coupled cells must be administered to induce tolerance, whereas suppression could be induced with as few as 10³ cells. In addition, the T cell tolerance was not sensitive to cyclophosphamide pretreatment, whereas the T cell suppression was cyclophosphamide sensitive. In contrast to T cell tolerance, suppressor T cells exerted their effects nonspecifically in the effector phase once they were stimulated with the inducing antigen.

In addition, a state of split responsiveness was demonstrated in animals given a subcutaneous (s.c.) injection of antigen-coupled cells. The s.c. route of induction resulted in a strong state of PFC nonresponsiveness while simultaneously priming for delayed type hypersensitivity (DTH) responses as assayed by footpad swelling. Thus, p-FG-coupled syngeneic spleen cells are capable of inducing: 1) T cell tolerance, 2) immune suppression, and 3) priming of DTH-reactive cells, depending on the conditions employed.

Footnotes

¹ This work was supported by Grants AI-14732 and AI-00152 from the National Institutes of Health, and Grant PCM 75-22422 from the National Science Foundation.