CD40-CD40 ligand interaction between dendritic cells and CD8+ T cells is needed to stimulate maximal T cell responses in the absence of CD4+ T cell help
Graduate School of Biomedical Sciences, Program in Immunology and Virology; Department of Pathology
Medical Subject Headings
Adoptive Transfer; Animals; Antigens, CD40; CD4-Positive T-Lymphocytes; CD40 Ligand; CD8-Positive T-Lymphocytes; Cell Communication; Dendritic Cells; Lymphocyte Activation; Mice; Mice, Knockout; Toll-Like Receptors
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
Stimulation of CD40 on APCs through CD40L expressed on helper CD4+ T cells activates and "licenses" the APCs to prime CD8+ T cell responses. Although other stimuli, such as TLR agonists, can also activate APCs, it is unclear to what extent they can replace the signals provided by CD40-CD40L interactions. In this study, we used an adoptive transfer system to re-examine the role of CD40 in the priming of naive CD8+ T cells. We find an approximately 50% reduction in expansion and cytokine production in TCR-transgenic T cells in the absence of CD40 on all APCs, and on dendritic cells in particular. Moreover, CD40-deficient and CD40L-deficient mice fail to develop endogenous CTL responses after immunization. Surprisingly, the role for CD40 and CD40L are observed even in the absence of CD4+ T cells; in this situation, the CD8+ T cell itself provides CD40L. Furthermore, we show that although TLR stimulation improves T cell responses, it cannot fully substitute for CD40. Altogether, these results reveal a direct and unique role for CD40L on CD8+ T cells interacting with CD40 on APCs that affects the magnitude and quality of CD8+ T cell responses.
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Citation: J Immunol. 2007 Mar 1;178(5):2844-52.