GIMAP Proteins in T-Lymphocytes

Abstract

(GIMAPs) GTPase of the immunity associated protein family are a novel protein family of putative small GTPases. GIMAPs are mainly expressed in the cells of the immune system and have been associated with immunological functions, such as thymocyte development, apoptosis of peripheral lymphocytes and T helper cell differentiation. GIMAPs have also been linked to immunological diseases, such as T cell lymphopenia, leukemia and autoimmune diseases. In this review we examine the role of GIMAP proteins in T-lymphocyte biology.

Figure 1

GIMAP gene clusters in human, mouse, and rat chromosomes. The GIMAP genes are clustered in human chromosome 7q36.1, mouse chromosome 6, and rat chromosome 4.

Figure 2

Thymocyte development. T-cells are developed in the thymus. The development can be defined by cell surface expression of CD4 and CD8. During the process, the thymosytes mature from CD4⁻CD8⁻ double negative (DN) cells into CD4⁺CD8⁺ double positive (DP) cells and finally into single positive (SP) CD4⁺ or CD8⁺ cells. The DN cells can be further categorized into DN1, DN2, DN3 and DN4 cells. ISP: immature single positive.

Figure 3

Apoptosis. Apoptosis can be initiated by the extrinsic or intrinsic pathways. The extrinsic pathway involves binding of ligands, such as tumor necrosis factor (TNF) or Fas ligand (FasL) to the death receptor. Subsequently, FAS-associating death domain (FADD) adapter protein is recruited to the receptor which leads to activation of caspase-8. The intrinsic pathway is initiated by cellular stress which induces loss of mitochondrial membrane potential, release of cytochrome C, and activation of caspase-9. The mitochondrial apoptotic pathway is controlled by the proapoptotic and antiapoptotic members of the Bcl-2 family. Cytochrome C release is inhibited by the prosurvival members Bcl-2/Bcl-xL and promoted by proapoptotic BAX/BIM. Both extrinsic and intrinsic pathways lead to activation of caspase-3 and, ultimately, cell death by apoptosis [40].

Figure 4

T-helper cell differentiation. Naïve Thp cells are able to differentiate into functional effector cell subsets according to the cytokine milieu. The differentiation process is initiated by antigen encounter. Naturally occurring regulatory T-cells are produced in the thymus. The different roles of the effector cells in the periphery are indicated in the figure.