ROLE OF THE THYMUS IN TOLERANCE
III. TOLF_~ANCS TO BOVI~ G~rM~ GLOBULIN AFTE1 DIRECT INJECTION OF
ANTIGEN INTO THE SHIE~LDED THYMUS OF IRKADIATED RATS*
BY PARKER J. STAPLES,~ M.D., IGAL GERY,§ PH.D.,AND BYRON H. WAKSMAN, M.D.
(From the Department of Microbiology, Yale University, New Haven, Connecticut)
(Received for publication 11 April 1966)
Several recent studies have directed attention to the possibifity that specific
immunologic tolerance, induced by antigen in newborn or irradiated adult ani-
mals, may result from interaction of antigen with immature lymphoid ceils in
central lymphatic organs such as the thymus (1-3). Nonaggregated proteins in-
troduced into the circulation enter the thymus readily, even in the adult (4--5),
and the thymus is generally recognized as a source of small lymphocytes which
participate in homograft immunity, delayed sensitivity, and some forms of anti-
Three times as many lymphocytes are found leaving the thymus as entering (6).
These seed peripheral lymphoid organs (7-9) and appear to act as precursors of the
large, pyroninophilic cells characteristic of the homograft response (10). Neonatally
thymectomized animals show a striking immunologic deficiency (7, 11, 12), which is
promptly corrected by supplying competent lymphocytes in sufficient number (13).
However thymus lymphocytes themselves appear to be incompetent, and some
maturation of these cells in the thymus must be postuated (13-15).
The present report describes an attempt to produce tolerance to bovine gam-
ma globulin by injecting this antigen directly into the thymus of adult rats, de-
prived of a competent pool of peripheral small lymphocytes by irradiation. The
results obtained confirm our earlier findings (1, 2) and provide support for the
Material and Methods
Lewis rats of both sexes (Microbiological Associates, Bethesda, Maryland), 6 wk of age at
the start of the experiment, were used throughout. They were maintained in groups of 5 in