The effects of pregnancy on the mouse thymic epithelium

Abstract

Changes in the murine thymus during pregnancy were studied using immunocytochemistry with monoclonal antibodies against thymic epithelial, neuroendocrine, and thymulin-producing cells, fibroblasts, blood vessels and connective tissue components. Extensive alterations occur in mid-pregnancy. The medulla was greatly enlarged in the involuted thymus, and there were greater numbers of epithelial cells. These epithelial cells had an altered distribution forming large structures surrounding spherical masses of mononuclear cells, lacked epithelial cells and often contained a central blood vessel with fibroblasts and connective tissue. We have called these structures 'medullary epithelial rings' (MERs). To our knowledge these structures have not been described before. Late in pregnancy the loss of the central mononuclear cells leaves collapsed structures in a smaller medulla that nevertheless retains many epithelial cells. In virgins and early-pregnancy, there are cortical channels free of epithelial cells that are very infrequent later in pregnancy. This may reflect the loss of steroid-sensitive thymocytes from the cortex. The influence of sex-steroids, neurological impulses and immune activity in causing the changes are discussed, as are the possible consequences in pregnancy of a reduced, thymocyte-depleted cortex and an enlarged medulla that shows great complexity and activity.

Thymic epithelial cells in age‐dependent involution

“…The altered function of cortical TEC and their relation to the cortical thymocyte population seems to be indicated also by an age-associated decrease in lymphoepithelial complexes of a TNC nature, isolated from mouse thymus by enzymatic digestion (Breliń ska et al, 1988). A similar manner of alteration was detected in the thymuses of pregnant rats in the course of transient involution of the organ, suggesting that some populations of TEC are probably eliminated by apoptosis (Breliń ska et al, 2002c;Clarke and Kendall, 1994b;Kendall and Clarke, 2000).…”

Abnormal T-Cell Reactivity against Paternal Antigens in Spontaneous Abortion

“…49,50 However, the thymus remains functional. 51,52 Moreover, the thymic involution seems to be a physiological process necessary for the success of normal pregnancy 52 and the placenta was proposed to be a crucial player in thymic involution by affecting thymocyte properties during their maturation in the thymic microenvironment. 48,53 Using an in vitro co-culture system, Savion and Toder 48 were able to show that placental or decidual explants from normal pregnant mice had inhibitory effect on thymocyte proliferation.…”

Eph/Ephrins-Mediated Thymocyte–Thymic Epithelial Cell Interactions Control Numerous Processes of Thymus Biology

“…These latter areas, of unknown significance, also exist in WT thymuses and in other mice with defects in molecules, such as Foxn1, Kremen 1, or Stat3, involved in TEC maturation ( 32 – 34 ), but are specially developed in EphB-deficient thymuses. They contain thymocytes and blood vessels, frequently surrounded by enlarged sheaths of connective tissue, and are different in cortex and medulla: the former ones contain thymocytes and some sheathed blood vessels, whereas in the medulla mTECs delimit areas with enlarged blood vessels, increased numbers of ER-TR7 + fibroblasts, components of the ECM (collagen IV, fibronectin, and laminin) ( 35 ), dendritic cells ( 36 ), and thymocytes in some areas ( 37 – 39 ).…”

“…EFAs are MHC class-II negative, little vascularized areas that contain abundant thymocytes frequently in division ( 39 ) reported as accumulations of DP thymocytes that do not undergo positive selection and will die subsequently by apoptosis ( 40 ). On the contrary, medullary epithelium-free areas that express several connective tissue markers could have a mesenchymal condition ( 35 ) and represent areas in which Eph-deficient TECs have undergone an epithelial–mesenchymal transition, losing their epithelial cell markers and acquiring a mesenchymal nature. In Eph mutant mice, EFAs could arise as a consequence of impeded intermingling and mutual exclusion of thymocytes and TECs caused by the lack of Eph–ephrin signaling as known in other systems ( 41 ).…”