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The Role of the Thymus during the Induction of Tolerance of a Thymus-Dependent Antigen¹

From the Department of Pathology and the Rheumatic Diseases Study Group, Department of Medicine, New York University School of Medicine, New York, New York 10016

Abstract

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.

Footnotes

¹ This work was supported by United States Public Health Service-National Institutes of Health Grants RO1-Al-09647 and PO1-AM-01431.

² Recipient of Research Career Development Award 1 KO4 A1-70653 from the National Institutes of Allergy and Infectious Disease.

³ Scholar of the Leukemia Society of America.