CD28 / TP44, a surface glycoprotein present on 80% of peripheral T cells in humans, has been shown to be an important costimulatory receptor in immune checkpoint pathway. This CD28/CD80/CD86 immune checkpoint pathway functions with a costimulatory signal transducing through CD28 / TP44 when T cells encounter an APC expressing either of the CD28 / TP44 ligands CD80 / B7-1 or CD86 / B7-2.
Due to costimulation of T cells, CD28 & CD80 (CD86) immune checkpoint pathway can affect multiple aspects of T cell activation. It will lower the concentration of anti-CD3 required to induce a proliferative response in culture. CD28 & CD80 (CD86) immune checkpoint pathway also markedly enhances the production of lymphokines by helper T cells through transcriptional and posttranscriptional regulation of gene expression, and can activate the cytolytic potential of cytotoxic T cells. Inhibition of CD28 & CD80 (CD86) immune checkpoint pathway in vivo can block xenograft rejection and allograft rejection is significantly delayed. In addition, transfection of B7 into a tumor cell line facilitates recognition and prevention of tumor growth.
Lawrence H. Boise et al. CD28 Costimulation Can Promote T Cell Survival by Enhancing the Expression of Bcl-xL. Immunity; 3: 87-98.
Salomon B et al. B7/CD28 Costimulation Is Essential for the Homeostasis of the CD4+CD25+ Immunoregulatory T Cells that Control Autoimmune Diabetes. Immunity. 2000;12(4):431-40.