Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F(1) (C57BL x C3H/Bi) mice. They occur within the lymphoid follicles of the spleen immediately surrounding the central arterioles, and constitute the mid and deep cortical zones of the lymph nodes. These depleted areas appear in healthy thymectomized mice as early as 3 wk after operation but, in mice which survive for more than 6 to 7 wk, the thymus-dependent areas are repopulated by rapidly dividing pyroninophilic cells, the majority of which are immature plasma cells. Syngeneic thymus cells, labeled in vitro with tritiated adenosine localize preferentially in the thymus-dependent areas after intravenous injection. Similarly labeled spleen cells also accumulate in these areas but, in addition, are distributed at the periphery of splenic follicles and in the outer cortical zone of the lymph nodes. Many more spleen than thymus cells enter the lymphoid tissues and the spleen appears to be the primary target. The apparent paradox that syngeneic thymus cells are less efficient than spleen cells in restoring neonatally thymectomized mice to normality is discussed in the light of these results and possible routes by which the migrating cells could enter the lymphoid tissues are considered. The origin of the plasma cells which repopulate the lymphocyte depleted areas is also discussed. It is concluded that the normal thymus produces cells which contribute directly to the migratory or circulatory lymphocyte population but that there also exists another source of supply for the plasma cell series. These two systems may function synergistically so that the thymus may control, directly or indirectly, the balance of cell populations within the body.

https://rupress.org/jem/article-pdf/123/1/191/1391872/191.pdf

Thymus-dependent areas in the lymphoid organs of neonatally thymectomized mice

Publisher Summary This chapter presents the mechanism of immunological paralysis. The paralysis is the result of a central failure of responsiveness brought about by exposure to antigen that prevents potentially competent cells from initiating a specific antibody response. In cellular terms, paralysis results from an adverse effect of antigen directly on lymphocytes, and the recovery from paralysis appears to involve the recruitment of new competent cells, not a recovery of responsiveness by once paralyzed cells. The quantitative factors involved in this antigenic exposure are determined, and these data not only shed light on the process of immunological paralysis but also on those conditions essential to the initiation of an antibody response. The barrier that the homograft reaction imposes to tissue transplantation can be overcome by paralyzing the host with donor antigens. This form of treatment that is already a routine procedure in animals provides the best hope of suppressing a homograft reaction without interfering with other immunological defenses. The chapter focuses on protein antigens, particularly heterologous serum proteins. These are of special interest because of their application in exploring the induction of paralysis in adult animals by low doses. The competent cell that is affected appears to be the lymphocyte. Macrophages in or from paralyzed animals function normally, but lymphocytes display altered reactivity. There is some evidence to suggest that antigen acts directly upon lymphocytes in the induction of paralysis.

The mechanism of immunological paralysis

A possible role for the lymphocyte in the mechanism of eosinopoiesis has been examined. Procedures known to deplete or inactivate the pool of recirculating lymphocytes such as neonatal thymectomy, administration of antilymphocyte serum, and prolonged thoracic duct drainage, either singly or in combination, resulted in a highly significant reduction in the eosinophil response to trichinosis. Irradiated animals exposed to parasitic challenge did not develop eosinophilia unless reconstituted with lymphocytes as well as bone marrow cells. When "memory" cells were used instead of normal lymphocytes, a "secondary" type of eosinophil response was observed. Transfer of a primary eosinophilia was achieved adoptively with a population of living large lymphocytes from thoracic duct lymph and peripheral blood, but not with blood plasma or cell-free lymph. The potency of the active lymphocytes was not impaired by enclosing them in cell-tight diffusion chambers, indicating that they exerted an effect on bone marrow by agency of a diffusible factor. The demonstration of a role for lymphocytes in induction of the eosinophil response to this kind of stimulus supports the conclusion that eosinophilia belongs in the category of immunologic phenomena.

https://rupress.org/jem/article-pdf/131/6/1288/1083692/1288.pdf

Mechanism of eosinophilia. II. Role of the lymphocyte.

T and B memory cells.

Publisher Summary The chapter discusses the ontogeny and phylogeny of adaptive immunity, including the acquisition of passive and active immunity by the developing fetus in relation to the phylogenetic development of active immunologic responses and relates immunologic capacity to the function of the thymus and of the bursa of Fabricus. The development of the lymphoid system plays a key role in development of the potential for adaptive immune response. Absence of the thymus during the period of development of the peripheral lymphoid tissues results in both abnormal lymphoid development and immunologic deficiency. In phylogeny, the data suggest that the transition to adaptive immunity occurs in the lower vertebrates and that it is paralleled by the development of a lymphoid thymus, other organized lymphoid tissues, and the lymphoid system of cells. The ontogenesis of immunity is discussed in terms of the following relationships and processes : interrelationship of fetus and mother, particularly serum immunoglobulin and antibody transfer; the beginning production of immunoglobulins during fetal and neonatal life; the origins of antibody-producing capacity and ability to initiate and express delayed allergic responses; the development of capacity for homograft rejection and the decrease of susceptibility to production of tolerance in the fetal and neonatal period; and the key role of the thymus and other central lymphoid tissue in the ontogeny of the lymphoid system and adaptive immunity. The studies of the lower fishes havenot been sufficiently comprehensive particularly with the more sophisticated methods of protein chemistry that are yielding such important information concerning the nature and interrelationships of the immunoglobulins.

Ontogeny and phylogeny of adaptive immunity.

The chronic drainage of lymph and cells from a thoracic duct fistula in rats results in a reduction in the weight of all the lymph nodes and of their content of small lymphocytes. The primary immune response to tetanus toxoid or sheep erythrocytes is severely depressed or abolished in such animals. This unresponsive state is related to the loss of lymphocytes from the thoracic duct fistula and, not to stress factors ensuing from the trauma of operation and restraint; it can be reversed by injecting inocula which contain almost exclusively small lymphocytes. In contrast to the severe impairment of the primary immune response in lymphocyte-depleted rats, such animals show a normal response to a second injection of tetanus toxoid. The mechanism by which small lymphocytes mediate the primary immune response is discussed.

https://rupress.org/jem/article-pdf/117/2/303/1080928/303.pdf

D. D. McGregor

Papers

The antibody response of rats depleted of lymphocytes by chronic drainage from the thoracic duct