Thymus



The Tissue atlas is based on immunohistochemical staining of tissue microarrays from 44 different normal tissue types. In addition to the standard setup, extended tissue profiling is performed for selected proteins, to give a more complete overview on where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye, thymus and additional samples of adrenal gland, skin and brain. For thymus, both full section samples and tissue microarrays with 1 mm diameter samples were used.

The full list of proteins analyzed in thymus is found in Table 1.


Histology


The thymus gland is primarily a lymphoid organ where the maturation of T cells occur, but it also produces several hormones. It is active in children, but after puberty the thymus undergoes involution, which involves replacement of the gland by adipose tissue and a decrease in lymphocytes.

The thymus is located beneath the sternum and consists of two lobes surrounded by a fibrous capsule. The lobes are divided by a fine septa into many lobules with an outer cortex with high cellular density and an inner medulla with lower cellular density. Hassall’s corpuscles are  structures only found in the thymic medulla that increase in number throughout life. These are non-secreting flattened thymic epithelial cells in a whorl-like formation arranged in concentric layers.


Function


T cells are a type of lymphocyte that is a part of the adaptive immune system together with B cells. T cells originate from hematopoietic cells in the bone marrow, which develop into immature thymocytes in the thymus. The thymocytes differentiate into several types of mature T cells; T helper cells, cytotoxic T cells, memory T cells, regulatory T cells and natural killer T cells. During maturation, T cells undergo β-selection and positive selection in the thymic cortex and negative selection in the thymic medulla. β-selection ultimately produces a functional αβ T cell receptor by rearranging the β-chain and pairing it with an constant α-chain. Before maturation, thymocytes do not express CD4⁺ or CD8⁺, this occurs during β-selection. After β-selection, thymocytes go through positive selection, where cells that are able to bind to MHC presented by thymic epithelial cells are selected for. During this process, thymocytes binding to MHC class II using CD4 as a coreceptor become CD4⁺ T cells (helper T cells), and thymocytes binding to MHC class I using CD8 as a coreceptor become CD8⁺ T cells (cytotoxic T cells). The final step of T cell maturation is negative selection, where autoreactive thymocytes are eliminated. T cells that bind too strongly to self-antigens presented on MHC complex of thymic epithelial cells receive an apoptotic signal. Remaining, now mature T cells, enter the bloodstream as naïve T cells.

Genes expressed specifically in CD8⁺ T cells


Examples of genes expressed in CD8⁺ T cells or during the maturation of CD8⁺ T cells include SATB1, PSMB11 and CD8B. SATB1 modulates genes that are essential in the maturation of CD8⁺ T cells (Figure 1).

Figure 1. Immunohistochemical staining of human thymus using an antibody toward SATB1 shows strong nuclear positivity.


PSMB11 generates peptides that are presented by MHC class I molecules during the maturation of CD8⁺ T cells in the thymic cortex (Figure 2).

Figure 2. Immunohistochemical staining of human thymus using an antibody toward PSMB11 shows strong cytoplasmic positivity in cortical cells and no positivity in medullary cells.


CD8B is the beta chain of the cell surface glycoprotein CD8. Acting as a coreceptor to the T cell receptor on the T cell, it recognizes MHC class I molecules displayed by an antigen presenting cell (Figure 3).

Figure 3. Immunohistochemical staining of human thymus using an antibody toward CD8B shows strong membranous positivity in cortical and medullary cells.



Table 1. The following 14 genes have been analyzed using extended thymus tissue samples.

Gene Gene description Staining pattern
ADORA2A Adenosine A2a receptor Strong membranous and cytoplasmic positivity was observed in a subset of medullary and cortical cells.
CCR8 C-C motif chemokine receptor 8 Cortical cells displayed strong cytoplasmic positivity. Weak to moderate staining was observed in a fraction of medullary cells,
CD8B CD8b molecule Strong membranous positivity was observed in thymic cortex and medulla.
FRMD1 FERM domain containing 1 Strong cytoplasmic postitvity was observed in medullary and cortical cells.
IL17REL Interleukin 17 receptor E like Strong cytoplasmic positivity was observed in subset of cortical and medullary cells.
MND1 Meiotic nuclear divisions 1 Strong membranous positivity was observed in medullary and cortical cells.
MZB1 Marginal zone B and B1 cell specific protein Strong cytoplasmic positivity was observed in a subset of medullary and cortical cells.
PSMB11 Proteasome subunit beta 11 Strong cytoplasmic positivity was observed in cortical cells. Medullary cells were negative.
RAD51 RAD51 recombinase Strong nuclear positivity was observed in cortical and medullary cells.
SATB1 SATB homeobox 1 Strong nuclear postitvity was observed in cortical and medullary cells.
SLAMF1 Signaling lymphocytic activation molecule family member 1 Strong cytoplasmic positivity was observed in a subset of medullary and cortical cells.
SLC46A2 Solute carrier family 46 member 2 Strong to moderate membranous positvity was observced in a subset of medullary and cortical cells.
THEMIS Thymocyte selection associated Strong cytoplasmic postitvity was observed in cortical and medullary cells.
UHRF1 Ubiquitin like with PHD and ring finger domains 1 Strong nuclear postitvity was observed in cortical cells and a subset of medullary cells.



Relevant links and publications


Uhlén M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419