The effect of neonatal thymectomy on the induction of tolerance of a thymus-dependent antigen was investigated. It was found that some thymectomized (Tx) rats failed to become tolerant after injection of sufficient bovine serum albumin (BSA) to make sham-thymectomized (STx) rats tolerant. This suggested that in the absence of the thymus, thymus-derived (T) cells already in the periphery before thymectomy, as well as bone marrow-derived (B) cells, failed to become tolerant. This hypothesis was tested by injecting mature T cells in the form of non-adherent, adult, syngeneic peripheral blood lymphocytes (PBL) during the period of tolerance induction. This increased the incidence of high responders to challenge in the Tx, BSA-injected (Tx-BSA) group while tolerance was again established in the STx-BSA group. Thymocytes did not substitute for the thymus in facilitating tolerance induction in PBL although thymocytes themselves appeared to become tolerant. Tx, saline-injected (Tx-Sal) recipients of mixtures of PBL and thymocytes made considerably higher responses to BSA than STx-Sal recipients of the same populations. These results suggest that thymocytes and PBL have different requirements for tolerance induction; the thymus itself or a sub-population of T cells, not adequately represented in PBL or thymocytes, exerts a suppressive effect both in the normal immune response and during tolerance induction.

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