[The role of the CD28 molecule in immunological tolerance]

The CD28 molecule is a glycoprotein presented mainly on T lymphocytes. It performs several functions in the organism, an important one being its role of costimulator for the activation of T lymphocytes. Binding with B7-1 (CD80) and B7-2 (CD86) ligands on antigen-presenting cells (APCs) induces the second signal essential for the activation of T lymphocytes and facilitates close apposition of the cell membranes of the APC and T cell. Costimulation through CD28 enhances the transcription and stability of IL-2 mRNA, the expression of Bcl-XL antiapoptotic molecules (thus supporting the proliferation of activated T lymphocytes), and also changes the polarization of Th lymphocytes towards the Th2 type. CD28 is mainly a positive regulator of T-cell activation, but it was also found to influence the negative selection of peripheral T lymphocytes. CD28 signals contributing to clonal expansion and effectory functions make T cells more sensitive to activation-induced cell death (AICD). When T lymphocytes are involved as a result of a strong TCR signal, the CD28 signal reduces the expansion of T cells, enhances apoptosis, and facilitates tolerance. CD8+ T lymphocytes, which lack the CD28 marker, play the role of regulatory cells. Blockade of the CD28-B7 interaction could be useful in preventing undesirable activation of the immune system in allergies, after transplantation, and in autoimmune diseases. Recently, more and more attention is being paid to anti-CD28 monoclonal antibodies and the possibilities of treating patients with autoimmune diseases and patients after transplantation.