Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

LY294002 and rapamycin co-operate to inhibit T-cell proliferation

Breslin, Elaine M., White, Paul ORCID:, Shore, Angharad M., Clement, Mathew ORCID: and Brennan, Paul ORCID: 2005. LY294002 and rapamycin co-operate to inhibit T-cell proliferation. British Journal of Pharmacology 144 (6) , pp. 791-800. 10.1038/sj.bjp.0706061

Full text not available from this repository.


1. T-cell proliferation is critical for mounting an effective adaptive immune response. It is regulated by signals through the T-cell receptor, through co-stimulation and through cytokines such as interleukin-2 (IL-2). Phosphatidylinositol 3-kinase (PI3K) lies downstream of each of these pathways and has been directly implicated in the regulation of lymphocyte proliferation. 2. In this study, we have shown that PI3K regulates cyclin D2 and cyclin D3, the first cell cycle proteins induced in T-cell proliferation, transcriptionally and post-transcriptionally. In T-lymphoblasts, LY294002, a PI3K inhibitor, prevents the induction of both D-type cyclin mRNA and protein, while rapamycin inhibits the induction of protein. Rapamycin inhibits mammalian target of rapamycin (mTOR), which lies downstream of PI3K. 3. Furthermore, our data show that the combination of LY294002 and rapamycin results in a co-operative inhibition of T-cell proliferation. This co-operation occurs in Kit225 cells stimulated with IL-2, and also in resting peripheral blood lymphocytes stimulated with antibodies to the T-cell receptor in the presence and absence of antibodies to CD28. 4. These data indicate that PI3K regulates T-cell proliferation in response to diverse stimuli, and suggest that combinations of inhibitors, perhaps isoform-selective, may be useful as alternative immunosuppressive therapies.

Item Type: Article
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
ISSN: 00071188
Last Modified: 06 Jan 2024 03:58

Citation Data

Cited 53 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item