CD40L Expression Allows CD8+ T Cells to Promote Their Own Expansion and Differentiation through Dendritic Cells

Abstract

CD8+ T cells play an important role in providing protective immunity against a wide range of pathogens, and a number of different factors control their activation. Although CD40L-mediated CD40 licensing of dendritic cells (DCs) by CD4+ T cells is known to be necessary for the generation of a robust CD8+ T cell response, the contribution of CD8+ T cell-expressed CD40L on DC licensing is less clear. We have previously shown that CD8+ T cells are able to induce the production of IL-12 p70 by DCs in a CD40L-dependent manner, providing some evidence that CD8+ T cell-mediated activation of DCs is possible. To better understand the role of CD40L on CD8+ T cell responses, we generated and characterized CD40L-expressing CD8+ T cells both in vitro and in vivo. We found that CD40L was expressed on 30–50% of effector CD8+ T cells when stimulated and that this expression was transient. The expression of CD40L on CD8+ T cells promoted the proliferation and differentiation of both the CD40L-expressing CD8+ T cells and the bystander effector CD8+ T cells. This process occurred via a cell-extrinsic manner and was mediated by DCs. These data demonstrate the existence of a mechanism where CD8+ T cells and DCs cooperate to maximize CD8+ T cell responses.

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

“…CD154 + CD8 T cells (also called CD8 helper cells) have been shown to support their own expansion and differentiation and to activate dendritic cells to promote antitumor immunity. 33 Although the RhoC 20mer contains an embedded HLA-A*03 binding peptide, we did not observe any CD8 T cell response (one single time point tested) in the two patients carrying the HLA-A*03 allele. 23 Since epitope spreading was shown to be associated with a better clinical outcome, 34 we also tested CD8 T cell reactivities against epitopes derived from PCa-associated antigens (PSA, PSMA, prostein, TRPP8 and survivin) in five HLA-A*02 patients.…”

Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help

“…In order to gain insight into the role of CD4 T cells on CTL activation, we studied the pathways by which CTL responses are triggered. One of the principal mechanisms by which CD4 T cells help the CTL cells priming is via licensing of DCs through the CD40-CD40L interactions, leading to maturation of DCs prior to their priming of CD8 T cells (43). In the absence of CD4 T cells, CD40 signaling can substitute the otherwise required T-helper signals, and the administration of agonistic anti-CD40 antibodies can improve vaccine efficacy in CD4 T-cell deficient conditions (34).…”

“…In the absence of CD4 T cells, CD40 signaling can substitute the otherwise required T-helper signals, and the administration of agonistic anti-CD40 antibodies can improve vaccine efficacy in CD4 T-cell deficient conditions (34). Moreover, a subset of CD8 T cells can express CD40L allowing an autocrine activation of CD8 T cells independent of T-helper cells (43). In the current study, we showed that PCI-based vaccination was CD4 T-cell independent, but that the T-helper signals were not substituted by CD40 signals, since CD8 T-cell responses were not impaired in CD40L-deficient mice.…”

Interactions between dendritic cells and T lymphocytes in pathogenesis of nasal polyps

“…CD1a is a marker of DCs and the double phenotypes of CD1a and CD40 used in the present study are specific DC markers. Furthermore, CD40+ staining indicates that DCs are in the mature phase and interacting with the T cells ( 11 ). The results of the present study indicate that the number of DCs in nITM tissue is significantly lower compared with NP tissues, which is consistent with previous reports ( 12 ) and suggests that DCs may serve an important role in the onset and development of NP.…”