Immune Defences of Teleost Fish - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 24

2.5.1 The thymus
About 500 million years ago, a new type of adaptive immune defence emerged in basal jawed
vertebrates, accompanied by morphological innovations, including the thymus. The thymus is
a primary lymphoid organ that is found in all vertebrates with the exception of jawless fish, such
as the lamprey, in which, however, discrete thymus-like lympho-epithelial structures, termed
thymoids, have been identified. The thymoids were found in the tips of the gill filaments and
the neighbouring secondary lamellae (both within the gill basket) of lamprey larvae. Only
in the thymoids the an expression of the orthologue of the gene encoding forkhead box N1
(FoxN1), a marker of the thymopoietic microenvironment in jawed vertebrates, accompanied
by expression of genes encoding type A variable lymphocyte receptors (VLRA) and cytosine
deaminase 1 (CDA1), found (Bajoghli et al. 2011).
The thymus first appears as an identifiable organ in the chondrichthyes and osteichthyes
(Rasmussen and Arnason 1999) and its emergence in evolution parallels the appearance of a
VDJ recombination as a novel means of somatically diversifying antigen receptors (Boehm and
Bleul 2007). The thymus has the unique capacity to support the development of self-tolerant
T cells expressing a diverse repertoire of antigen receptors and the production of self-restricted
T cells (Manley 2000) providing the appropriate microenvironment. Generally, the thymus
develops in the lamina propria of the gastrointestinal tract (GIT) in pouches located at the
base of the gill arches; its development can be traced through evolution, beginning in early
fish species as a thickening in the epithelium of the pharyngeal area of the GIT. In teleosts
the thymus appears as a pair organ located dorsally beneath the operculum and covered by a
mucosal epithelium (Zapata and Amemiya 2000; Matsunaga and Rahman 2001; Bowden etal.
2005; Langenau and Zon 2005). Its parenchyma consists of lymphocytes, macrophages, den-
dritic/interdigitating cells and myoid cells, while the stroma is composed of cells of epithelial
morphology (Zapata et al. 1996).
Anatomical studies demonstrated that the differentiation of the thymic structure is highly
variable among fish species (Bowden et al. 2005). In fact in many fish there are no clear zones
to the thymus (Luer et al. 1995; Liu et al. 2004), while in European sea bass (Abelli et al.
1994), turbot Scophthalmus maximus (Fournier-Betz et al. 2000), zebrafish (Danilova et al.
2004), halibut Hippoglossus hippoglossus (Bowden et al. 2005), rainbow trout (Fisher et al.
2005), common carp (Huttenhuis et al. 2005) and Atlantic salmon (Koppang et al. 2003),
studies have observed a distinction between outer (cortex) and inner (medulla) regions of
the thymus, even if the lack of a corticomedullary junction persists. The thymus possesses a
capsule of epithelial cells enclosing a cortex of lymphoid tissue within which are lymphocytes
whose normal development is dependent upon cell interactions with thymic stroma and
secreted molecules. The capsule invaginates into the organ producing trabeculae giving
passage to capillaries (Manley and Blackburn 2003) and enclosing a 3D structure that is
considered important for positive selection (affinity to MHC) to allow sufficient interaction
with the MHC molecules of the reticular epithelium. In this respect the expression of MHC
class I and II molecules found in rainbow trout thymus suggested a possible role to mediate
the acquisition of a T cell repertoire by participating in the positive and negative selections
of thymocytes (Fisher et al. 2005). In teleosts, the thymic microenvironment is the site of T
cell maturation in a dynamic process that, as described in mammals, is fed by the recruitment
of early thymocyte progenitors from the bloodstream and culminates in the export of mature
thymocytes back into circulation (Ladi et al. 2006). In zebrafish, it has been well documented
that early steps in T cell (thymocyte) development and thymic organogenesis are similar in