**5. Foxn-1 expression**

Thymic epithelial cell-specific transcription factor, Foxn-1, shows scattered positive cells in both the cortex and medulla and line up along the thymic capsule and PS (**Figures 8** and **14**). The density of Foxn-1-positive cells seems to be higher in the medulla than in the cortex. Double staining with anti-cytokeratin and anti-Foxn-1 antibodies shows that Foxn-1 is expressed in both medullary compartments; namely, Foxn-1 positive cells are present in the EFA (**Figure 15**).

Acute thymic atrophy can be induced by Foxn-1 disruption [29]. Foxn-1 is necessary for the differentiation of both cortical and medullary epithelial cells [27, 47–49]. By age the number of Foxn-1-expressing epithelial cells seems to decrease [49], and this change may be paralleled with the diminished occurrence of the EFA. In elderly people, the risk of autoimmune disease is increased that may be in connection with the accumulation of Foxn-1-negative epithelial cells [49, 50] or the increased number of Foxn-1-expressing mesenchymal cells and decreased volume of EFA. However, in addition to the increasing number of Foxn-1-negative

**17**

*anlage.*

**Figure 16.**

*Compartmentalization of Human Thymic Medulla: Facts and Hypotheses*

epithelial cells, Foxn-1 is expressed in the KNA, that is, in non-epithelial cells with

*Double staining: cytokeratin (red) and Foxn-1 (green). Foxn-1-positive cells are present in both the KPN and* 

In the epithelium-free areas, several vessel-associated cells like pericyte and smooth-even-striated muscle cells develop from neural crest cells. It is reasonable to assume that the reticular tissue of epithelium-free area also develops from neural crest cells. In addition to this hypothesis, it is remained also unsolved if the mesenchymal cells or abnormal (keratin-free) epithelial cells express Foxn-1 transcription factor. In mouse and chicken, where the thymus develops solely from the endodermal pouch epithelium, the cortical cells enter the medulla, sort out, and

*Scheme: (a) from the ectodermal cervical sinus, the cervical vesicle (dark green) separates and attaches to the corresponding third branchial pouch (red), which descends into the upper mediastinum (b). (I–V, pharyngeal pouches; 1–4, pharyngeal groves). Ventral region of the third pharyngeal pouch (red) gives the endodermal part of the thymus. Part of the cervical vesicle (ectoderm, green) contributes to the thymic* 

*DOI: http://dx.doi.org/10.5772/intechopen.88588*

unknown consequences (**Figure 15**).

**6. Conclusions**

*EFA of the thymic medulla.*

**Figure 15.**

**Figure 14.** *Thymus 5. Age 16 months: Foxn-1-positive cells outline the thymic lobuli.*

*Compartmentalization of Human Thymic Medulla: Facts and Hypotheses DOI: http://dx.doi.org/10.5772/intechopen.88588*

#### **Figure 15.**

*Thymus*

into the medulla. This finding may be confirmed by monoclonal antibodies (mAb(s)) (RCK 105 and RGE5) which recognize cortical epithelial cells and some medullary ones [7]. These experiments may show that cortical epithelial cells enter the medulla. Furthermore, MTS29 mAb stains isolated in medullary epithelial cells. The antigen was also present in the epidermal epithelium [4]. The marginal cells of the corpuscle are alive and perhaps temporarily capable of producing SBP (**Figure 12**) and/or other biological active substances. If we adopt the double-germ layer origin of thymic epithelial cells, then both type II pneumocytes (SPB-producing cells) and the cortical stellate cells and cells of Hassall's body are in "foreign environment" of the medulla. The surface of the cell provides important information for the neighboring cell to form tissue and organs. According to the law of thermodynamic stability, if *in vitro* two types of cells are mixed and the bond among different cells is weaker than among homotypic cells, then the cells are sorting out and the homotypic cells aggregate [45]. Possibly, this is the situation *in vivo*, in case of Hassall's body formation. Several cortical cells enter the medulla and sort out, aggregating in the form of Hassall's body. The SPB-producing type II pneumocytes have got a similar situation as cortical epithelial cells; therefore the SPB-producing cells also sorting out "join" to the Hassall's bodies,

Thymic epithelial cell-specific transcription factor, Foxn-1, shows scattered positive cells in both the cortex and medulla and line up along the thymic capsule and PS (**Figures 8** and **14**). The density of Foxn-1-positive cells seems to be higher in the medulla than in the cortex. Double staining with anti-cytokeratin and anti-Foxn-1 antibodies shows that Foxn-1 is expressed in both medullary compartments;

Acute thymic atrophy can be induced by Foxn-1 disruption [29]. Foxn-1 is necessary for the differentiation of both cortical and medullary epithelial cells [27, 47–49]. By age the number of Foxn-1-expressing epithelial cells seems to decrease [49], and this change may be paralleled with the diminished occurrence of the EFA. In elderly people, the risk of autoimmune disease is increased that may be in connection with the accumulation of Foxn-1-negative epithelial cells [49, 50] or the increased number of Foxn-1-expressing mesenchymal cells and decreased volume of EFA. However, in addition to the increasing number of Foxn-1-negative

namely, Foxn-1 positive cells are present in the EFA (**Figure 15**).

*Thymus 5. Age 16 months: Foxn-1-positive cells outline the thymic lobuli.*

resulting in SPB-positive Hassall's corpuscles [46].

**5. Foxn-1 expression**

**16**

**Figure 14.**

*Double staining: cytokeratin (red) and Foxn-1 (green). Foxn-1-positive cells are present in both the KPN and EFA of the thymic medulla.*

epithelial cells, Foxn-1 is expressed in the KNA, that is, in non-epithelial cells with unknown consequences (**Figure 15**).

#### **6. Conclusions**

In the epithelium-free areas, several vessel-associated cells like pericyte and smooth-even-striated muscle cells develop from neural crest cells. It is reasonable to assume that the reticular tissue of epithelium-free area also develops from neural crest cells. In addition to this hypothesis, it is remained also unsolved if the mesenchymal cells or abnormal (keratin-free) epithelial cells express Foxn-1 transcription factor. In mouse and chicken, where the thymus develops solely from the endodermal pouch epithelium, the cortical cells enter the medulla, sort out, and

#### **Figure 16.**

*Scheme: (a) from the ectodermal cervical sinus, the cervical vesicle (dark green) separates and attaches to the corresponding third branchial pouch (red), which descends into the upper mediastinum (b). (I–V, pharyngeal pouches; 1–4, pharyngeal groves). Ventral region of the third pharyngeal pouch (red) gives the endodermal part of the thymus. Part of the cervical vesicle (ectoderm, green) contributes to the thymic anlage.*

form Hassall's bodies. In human thymus Hassall's corpuscles are large (compound structures), while in mouse and chicken, Hassall's bodies are small. The differences in Hassall's bodies may be related with the double- and/or single-germ layer origin of the thymic epithelial anlage (**Figure 16**).
