Thymus-Dependent Areas in the Lymphoid Organs of Neonatally Thymectomized Mice

Abstract

Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F1 (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.

Cell to Cell Interaction in the Immune Response

“…The spleens of these mice were much larger than those of thymectomized irradiated mice. It is possible that the larger spleens trap more thymus cells since these cells preferentially home there rather than to lymph nodes (24,25). Thoracic duct cells, however, have a capacity to recirculate and to home to all the lymphoid tissues (26).…”

How One Thing Led to Another

“…I found dramatic and incontrovertible evidence of high levels of thymus cell migration into blood and immediately into specific zones of lymph nodes, Peyer patches, and spleen-more dramatic when newborn rats were labeled than when adult rats were labeled, but with the same patterns (25). [While on a visit to Mill Hill, I showed my data to Delphine Parrott, who was noting the absence of those zones in thymectomized mice, and she called them thymus-dependent zones of lymphoid secondary organs (26,27).] I showed that the migrants contained cells that could become activated lymphocytes, using Gowans' method of showing the transition of small lymphocytes to large pyroninophilic cells upon alloimmunization.…”

“…I showed that the migrants contained cells that could become activated lymphocytes, using Gowans' method of showing the transition of small lymphocytes to large pyroninophilic cells upon alloimmunization. These studies provided the conclusion that the thymus is primarily responsible for the seeding of immunocompetent naive T cells that selectively homed via specialized lymph node and Peyer patch high-walled endothelial postcapillary venules (HEVs) [first described by Gowans as the sites of lymphocyte recirculation from blood to lymphoid organs and back via lymphatics and the thoracic duct to blood (10) into peri-HEV T cells zones, excluding the B cell follicles we later described (26,(28)(29)(30)]. The immigrating thymic migrants could meet antigen and begin the response to antigens that had filtered into LNs, PPs, or spleens (31).…”

The Lymph Node Revisited: Development, Morphology, Functioning, and Role in Triggering Primary Immune Responses

“…A striking example is an initial report that lymph nodes of thymectomized mice ''showed no proper structures and no plasma cells, often being reduced to a small piece of adipose tissue'' (Miller, 1962). Reports followed stating instead that the deep cortex of the lymph nodes of thymectomized mice is devoid of lymphocytes, hence, it was called a ''thymusdependent zone'' (Parrott et al, 1966) but also a ''T cell area'' or a ''paracortex'' (Goldschneider and McGregor, 1973), however, these terms still conveyed partly unrealistic concepts. The term ''thymus-dependent zone'' is a misnomer (Fossum, 1990) because the deep cortex does form in athymic animals, except that its center is devoid of T cells while its periphery is still populated by B cells (Sainte-Marie et al, 1984).…”