CD28 (Cluster of Differentiation 28) is a homodimeric stimulatory cell surface receptor of the immunoglobulin (Ig) superfamily that is located on the chromosome 2q33.2. It is expressed on naive T cells and has also been found on the surface of plasma cells, eosinophils, and neutrophils. CD28 remains the most extensively studied costimulatory molecular and is a primary one for T-cell activatio. The control of T-cell responses through CD28 co-stimulation provides a means of anti-self and antimicrobial immunity. CD28 is essential for the lymphocyte activation and survival. A number of antigen-experienced T-cells lose CD28, and then can be re-activated without its engagement. Diseases linked to CD28 involve mycosis fungoides and Sezary's disease and the related pathways are Th2 differentiation pathway and RET signaling. CD40 (Cluster of differentiation 40), also referred to TNFRSF5, is a 48 kDa phosphorylated glycoprotein encoded at the chromosome of 20q13.12 and contains 277 amino acids. This type I transmembrane protein is originally characterized on B cells, and later found on platelets, monocytes, macrophages and dendritic cells, as well as on non-hematopoietic cells including fibroblasts, myofibroblasts, epithelial and endothelial cells. The CD40 receptor on antigen-presenting cells of the immune system and important for mediating a variety of immune and inflammatory processes including memory B cell development, T cell-dependent immunoglobulin class switching, and germinal center formation. CD40 has a ligand known as CD40L or CD154, a type II transmembrane protein, composed of a sandwich extracellular structure and belonging to the TNF superfamily.