T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions

  title={T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions},
  author={Stephen P. Schoenberger and Rene Everardus Maria Toes and Ellen van der Voort and Rienk Offringa and Cornelis J M Melief},
Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper lymphocytes,, the nature of the ‘help’ provided to CTLs is unknown. One widely held view is that help for CTLs is mediated by cytokines produced by T-helper cells activated in proximity to the CTL precursor at the surface of an antigen-presenting cell (APC). An alternative theory is that, rather than being directly supplied to the CTL by the helper cell, help is delivered… 

Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes

An in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide–specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4+ T helper cells found that CD4 + T cells can provide potent help for DCs to activate CD8+ T cells when antigen is provided.

CD 40-independent Pathways of T Cell Help for Priming of CD 8 1 Cytotoxic T Lymphocytes

An in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide–specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4 1 T helper cells found that CD4 2 T cells can provide potent help for DCs to activate CD8 1 T cells when antigen is provided.

The role of CD40 in peripheral T cell tolerance and immunity

Intervention of CD40–CD40L interactions can result in enhancement or down-modulation of T cell reactivity and therefore modulation of these interactions may form the foundation of new treatment modalities directed against malignancies, allergies, organ rejections and autoimmunity.

The critical role of CD40/CD40L in the CD4‐dependent generation of CD8+ T cell immunity

It is important that CD40 and its ligand, CD40L, have been implicated in the provision of this help and, in particular, the generation of long‐lasting CTL memory.

CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes

The results demonstrate that T-cell help is ‘programmed’ into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen.

CD8 T cell priming by B lymphocytes is CD4 help dependent

In vitro experiments found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help, and point to the previously unappreciated fact that the induction ofCD8 T cell responses by B lymphocyte requires Tcell help.

Direct demonstration of CD4 T cell cooperation in the primary in vivo generation of CD4 effector T cells.

It is demonstrated that the activation of CD4 T cells, specific for the hen egg lysozyme (HEL)(105) (-120) peptide, is optimally achieved when BALB/c mice are immunized with additional MHC class II-binding HEL peptides in incomplete Freund's adjuvant.

Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells

The ability of class I-restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections.

CD8 T lymphocyte mobilization to virus-infected tissue requires CD4 T-cell help

The results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells.



Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help

It is shown that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells, and it is argued that the cognitive nature of this event suggests that theCD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

CD40 ligand-transduced co-stimulation of T cells in the development of helper function

It is shown that co-stimulation of T cells through CD40 ligand causes their differentiation into cells that help B cells to make mature antibody responses and togenerate memory populations.

CD40 Ligand-Dependent T Cell Activation: Requirement of B7-CD28 Signaling Through CD40

CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.2 on spleen cells.

Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice.

It is demonstrated that animals deficient in CD40L expression display a deficiency in T cell-dependent macrophage-mediated immune responses, similar to that shown in knockout mice.

Induction of B cell costimulatory function by recombinant murine CD40 ligand

It is shown that recombinant membrane‐bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4+ Tcells and suggested that CD40 L‐activated B cells express an additional costimulation activity that is not associated with LPS‐ activated B cells.

Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand

Adoptively transferred antigen-specific CD4+ T cells lacking CD40L failed to expand upon antigen challenge of the recipients, showing that expression ofCD40L on T cells is required for in vivo priming of CD4 + T cells and therefore for the initiation of specific T-cell immune responses.

The dendritic cell system and its role in immunogenicity.

Dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells.

Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.

A critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines is suggested and may have important implications for future approaches to cell-based cancer therapies.

Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation

It is found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12, which is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs.

CD40L is important for induction of, but not response to, costimulatory activity. ICAM-1 as the second costimulatory molecule rapidly up-regulated by CD40L.

It is shown that CD40L is not essential for T cell response to TCR engagement if the APC have costimulatory activity, although it is essential forT cell-mediated induction of such costimulation activity.