The complexities of CD28 and CTLA-4 signalling: PI3K and beyond
- PMID: 10202558
The complexities of CD28 and CTLA-4 signalling: PI3K and beyond
Abstract
A successful immune response requires a set of non-cognate cell-cell interactions which provide the second "costimulatory" signal to the T cells. The best characterized costimulatory receptor expressed on resting T cells is CD28 which provides poorly-defined cyclosporin-resistant biochemical signal(s) that promote expression of several cytokines/chemokines. Another major effect of CD28 ligation is the promotion of cell survival which is thought to occur via the up-regulation of Bcl-xL expression, CD28 shares its ligands B7.1 and B7.2 with the related CTLA-4, which plays an inhibitory role in T cell activation. Manipulation of CD28/CTLA-4 interactions with their natural ligands has provided exciting results in transplantation and tumor therapy settings and also has potential in the treatment of several diseases such as arthritis and multiple sclerosis, asthma and protection against HIV infection. The biochemical basis for the different functional outcomes of CD28 and CTLA-4 ligation has been the subject of intense investigation over the past few years. This review will focus on our current understanding of the biochemical signals that may be involved in regulating the different functional outcomes of CD28 and CTLA-4, with particular emphasis on the role played by the PI3K-dependent signalling cascade.
Similar articles
-
Expression and functional significance of CTLA-4, a negative regulator of T cell activation.Arch Immunol Ther Exp (Warsz). 2001;49(1):39-46. Arch Immunol Ther Exp (Warsz). 2001. PMID: 11266089 Review.
-
Costimulation of T lymphocytes with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 induces functional expression of CTLA-4, a second receptor for B7.J Immunol. 1994 Mar 15;152(6):2686-97. J Immunol. 1994. PMID: 7511623
-
Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells.J Immunol. 1999 Jun 1;162(11):6368-77. J Immunol. 1999. PMID: 10352249
-
CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production.J Immunol. 1992 Dec 15;149(12):3795-801. J Immunol. 1992. PMID: 1281186
-
CD28: a signalling perspective.Biochem J. 1996 Sep 1;318 ( Pt 2)(Pt 2):361-77. doi: 10.1042/bj3180361. Biochem J. 1996. PMID: 8809021 Free PMC article. Review.
Cited by
-
Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases.Br J Pharmacol. 2000 Oct;131(4):811-9. doi: 10.1038/sj.bjp.0703636. Br J Pharmacol. 2000. PMID: 11030732 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Research Materials
Miscellaneous