Use of Cultured Thymic Tissues for the Regeneration of the Thymus

Abstract

An account of research conducted on the transplantation of thymic cells and tissues in order to restore the functional activity of the thymus is reviewed, and discussed in the context of current concepts. Although most rodent work has been conducted on the transplantation of cultured fragments under the kidney capsule, human transplantation studies and models have used other sites or other species such as the severe combined immunodeficient mouse as hosts. The factors affecting the growth of thymic cells in culture is considered in detail since the methodology can strongly influence the cells favoured under culture conditions. An extension of this work to characterize both thymic fragments implanted under the kidney capsule of rats and cultured thymic cells has recently led to the appreciation that the adult thymus must contain a small number of neural crest-like cells. These cells have a high level of proliferation in the implanted fragments, expand in culture, and belong to a family of cytokeratin-positive cells exhibiting immunoreactivity for a wide range of neuropeptides and transmitters. Thus primary cultures of thymus can contain a wide range of glia-like cells.This can be explained by the fact that the thymus, in addition to having a mesenchymal neural crest component, is probably derived from cardiac neural crest. Closely associated neural crest also has glia-like properties (the supporting cells of the enteric nervous system). These finding can account for the large number of reports of epithelial cells of the adult thymus being immunoreactive to antibodies raised to neuroendocrine and neurotransmitters. Neuroimmune interactions in the thymus are more fundamental than previous work had suggested.

Transplantation Tolerance and Autoimmunity After Xenogeneic Thymus Transplantation

“…The Journal of Immunology, 2001, 166: 1843-1854. T he thymus is well known to play critical roles not only in establishing and shaping a functional T cell repertoire, but also in inducing and maintaining self-tolerance as well as deletional transplantation (Tx) 3 tolerance (1,2). Either isogeneic or allogeneic thymus (allothymus) tissues have been shown to restore thymus-dependent immunity such as reactivity to mitogens or allogeneic Ags and the ability of IgG Ab production in congenitally athymic or neonatally thymectomized animals.…”

“…Either isogeneic or allogeneic thymus (allothymus) tissues have been shown to restore thymus-dependent immunity such as reactivity to mitogens or allogeneic Ags and the ability of IgG Ab production in congenitally athymic or neonatally thymectomized animals. Additionally, allothymus-reconstituted animals become tolerant to donor strain graft and resistant against third-party allograft (3).…”

Expression of parathyroid hormone‐related protein and the parathyroid hormone/parathyroid hormone‐related protein receptor in rat thymic epithelial cells

“…TEC, in addition to their obvious similarities to and possible derivation from neuroectodermal cells (Jones et al 1999) have also been postulated to have similarities with the cells of the epidermis (DeWaal & Rademakers, 1997). It is therefore not surprising that PTHrP, in addition to being expressed in TEC, is also expressed by cells in all layers of the epidermis, as well as in cultured keratinocytes (Atillasoy et al 1991 ;Philbrick et al 1996).…”