**3. Migration**

Circulation of T cell in the blood, secondary lymphoid organs, and nonlymphoid tissues is a complex system. Numerous receptors, ligands, chemokines, cytokines, and transcription factors has a role on this [31, 32]. T cells can be classified according to the organs or tissues in which they recirculate. Schematic illustration for migration of T cell subsets is shown in **Figure 2**.


CC-chemokine receptor 7 (CCR7), CD69, CD49, S1PR1, KLF2, and integrins are the main factors responsible for the migration of T cell subsets. The role of these factors may differ depending on the location of the host tissue [68, 69]. These will be further explained in more detail in phenotype and localization parts.

**53**

**4.3 CD49a**

*Resident Memory T Cells*

**4. TRM markers**

**4.1 CD103**

**4.2 CD69**

*DOI: http://dx.doi.org/10.5772/intechopen.90334*

CD44 have been widely investigated.

tant for T lymphocyte adhesion and stimulation [71].

T cells such as CD4 CD103 T cells and CD8 CD103 Treg cells.

TRM differentiation as well as activation of the immune response.

but it is not sufficient to be the sole determinant.

laminin such as ColIV and ColI [9, 80, 81].

In order to distinguish TRM cells from other T cell subsets, in most of the studies in both mice and humans, identification markers such as CD103, CD69, Cd49a, and

αEβ7 integrin (CD103) was first discovered in the late 1980s. After that several

Following the discovery of the ligand called E-cadherin, interest in CD103 has been increased considerably. E-cadherin is a transmembrane protein with an extracellular region containing extracellular cadherin domain repeats, which mediates cell-cell adhesion by homodimerizing in trans with E-cadherin domains of neighboring cells [72]. CD103 is important in adhesion as well as T cell activation and TGF-B induced defense in tumor microenvironment. In TGF-B environment, CD103 TRM cells have been shown to release more efficient granzyme. Although CD103 is an important marker, CD103 alone is not sufficient to detect TRM cells. CD103 negative TRM cells were found in several tissues. Furthermore, there are different types of CD103

CD8+ TRM cells can be characterized by their expression of the surface molecules CD69 and CD103. These markers are usually not expressed on circulation T cells [73]. CD69 is a type II C-lectin membrane receptor with a scarce expression in resting lymphocytes that is rapidly induced upon cell activation [74]. Because of these features, CD69 was considered as early activation antigen of immune cells. However, recent studies have shown that this molecule is an important indicator of

CD69 has been found to suppress the activity of sphingosine-1 phosphate receptor 1 (S1P1), helping the TRM cells that remain in peripheral tissues [75]. The S1P1 receptor/gene, originally known as endothelial differentiation gene 1, acts by binding with a bioactive signaling molecule S1P1 [76]. It was suggested that CD69 expression might help retaining TRM cells in peripheral tissues by suppressing the activity of S1P1. Decreased expression of transcription factor of KLF2 is another factor affecting S1P1 expression to remain down-regulated in TRM cells [77, 78]. Moreover, CD69 expression is not limited to TRM cells and is not essential for TRM formation. CD69 has also been shown to be expressed in cells such as natural killer cells, dendritic cells, and in the absence of CD69, TRM formation decreased but is not completely eliminated [32, 79]. Therefore, CD69 is a good TRM marker,

CD49a or integrin α1 paired with CD29 (integrin-β1) to form very late antigen

(VLA-1). VLA-1 is a collagen-binding integrin and receptor for collagen and

new monoclonal antibodies were produced as a specific marker for intestinal intraepithelial T cells in humans, mice, and rats, presumably contributing to their tissue-specific localization [70]. Integrins are transmembrane αβ heterodimers that bind to extracellular matrix components and to cellular counter receptors. They have important roles on cell localization, migration, and signaling and are impor-

**Figure 2.** *Schematic illustration of circulation and migration of T cell subsets.*
