Thymic Lymphopoiesis and Cell Loss in Newborn Mice

Abstract

Thymic lymphopoiesis in 2 day old Swiss albino mice (Hale-Stoner strain) was studied autoradiographically based on the variation of mitotic labeling indices and intensities after a single intraabdominal injection of 3H-thymidine. Best estimates for the duration of various phases of the generative cell cycle are as follows: G2 for the majority of cells: 86-94 minutes, shortest possible duration for a small fraction of cells: 35-48 minutes; mitosis: 27-44 minutes; DNA synthesis: 7 hours; generation time: 9¼ hours. G1 could not be determined directly by the methods used but probably is short. The present data do not indicate different generation times for proliferating thymic lymphoid cells of unequal size although the very largest elements must be excluded from this statement because of rare occurrence. The results obtained in this study together with data on changes of thymic weight and proliferative activity in the neonatal period indicate that during the third day after birth, a fraction corresponding to one third of all lymphoid cells present in the organ at the end of this period is lost. In view of the extremely low pyknotic index in the thymus at this age, the present data provide support in favor of an extensive emigration of lymphoid cells being the major cause of this cell loss.

Magnitude and Pattern of Thymic Lymphocyte Migration in Neonatal Mice

“…Within 2 or 3 days of postnatal life, however, there is a marked increase in the number of lymphocytes in these tissues. Kinetic studies suggested that during this same developmental period a large number of cells leave the thymus (19). In the present study a modified technique of local labeling of the thymus was used in neonatal mice and the migration of labeled cells to spleen, Peyer's patches, lymph nodes, and bone marrow was followed with time.…”

“…It has been postulated that an overwhelming majority of thymic lymphocytes disintegrate within the thymus (17). Kinetic studies on mice, however, have provided support for an extensive migration of lymphoid cells from the thymus to peripheral lymphoid organs in the neonatal period (18)(19)(20). Experiments in the calf utilizing both continuous intra-arterial infusion of the thymus with tritiated thymidine and thymus-specific antigen as markers have indicated that a substantial peripheralization of thymic lymphocytes is maintained beyond the neonatal period (21).…”

Comparative Light and Electron Microscopical Studies of Decaying Thymic Lymphoid Cells

“…TQ day it is generally accepted that the majority of cells produced in tlie thymus decay in situ while a minority leave the organ (Everett & Tylor 1970). It must be admitted, however, that the number of pyknotic thymocytes seen under normal conditions is too low to explain such an extensive degree of cell death (Nakamura & Metcalf 1961, Sainte-Marie & Leblond 1964, Michalke et al 1969. For this reason Metcalf & Brumby ( 1966) proposed another theory of thymocyte degeneration: the "thymocyte explosion" which being invisible, cannot be observed in the light microscope (Metcalf 1966).…”

Study of Functional Lymphocyte Populations with Heterologous Antisera

“…The total life span of cells in the thymus has been estimated by several groups to be 3 days or less (Weissman 1967, Craddock et al 1964, Matsuyama et al 1966, Ernstrom & Sandberg 1970. Cell division is limited mainly to medium and large cells, the cycle time beî ng as short as 9.5 hours (Michalke et al 1969). As shown in Table X, characteristic attributes of immunocompetent peripheral lymphocytes, notably the abihty to recirculate and to respond to mitogens such as PHA and to specific antigens with MLR in vitro and GVH in vivo, were all found limited to fraction C (Colley et al 1970b).…”

“…Metcalf and his colleagues showed several years ago, in studies of adult mice with multiple thymus grafts labelled with tritiated thymidine (Matsuyama et al 1966), that a high proportion of thymocytes fail to emigrate and die within the thymus. (However, in neonatal animals, there is little cell death within this organ (Michalke et al 1969).) Emstrom & Sandberg (1970) have calculated, from precise kinetic data, that only 27 per cent of thymocytes produced in the adult guinea pig thymus are exported via the thymus veins.…”