| First Author | Murugaiyan G | Year | 2007 |
| Journal | Clin Exp Immunol | Volume | 149 |
| Issue | 1 | Pages | 194-202 |
| PubMed ID | 17488293 | Mgi Jnum | J:123479 |
| Mgi Id | MGI:3718723 | Doi | 10.1111/j.1365-2249.2007.03407.x |
| Citation | Murugaiyan G, et al. (2007) Levels of CD40 expression on dendritic cells dictate tumour growth or regression. Clin Exp Immunol 149(1):194-202 |
| abstractText | Tumour regression requires activation of T cells. It has been shown that the interaction between T cell-expressed CD40-ligand (CD40-L) and antigen-presenting cell-expressed CD40 plays a crucial role in T cell activation. CD40-L- or CD40-deficient mice are susceptible to tumour growth. CD40-based therapies are also shown to control tumour growth significantly, suggesting that CD40-CD40-L interaction induces anti-tumour T cell responses and tumour regression. We demonstrate that the anti-tumour T cell response can be modulated reciprocally as a function of the levels of CD40 expression. At low expression levels, CD40 promotes tumour growth; at higher expression levels, CD40 induces tumour-regressing T cell response. Dendritic cells (DC) sorted onto major histocompatibility complex (MHC)-II expression are found to be similar in CD40 and CD80 expression. The MHC-II(hi)/CD40(hi) DC induce interleukin (IL)-12-dominated and T helper 1 (Th1)-type response, whereas MHC-II(lo)/CD40(lo) DC promote high IL-10 and Th2-type T cells. The T cells induced by these DC also differ in terms of regulatory T cell markers, lymphocyte activation gene-3 (LAG-3) and glucocorticoid-induced tumour necrosis factor (TNF) receptor family-related gene (GITR). Thus, we report for the first time that CD40-induced effector T cell response depends on CD40 expression levels in vivo. |
