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B7/CD28-dependent and -independent induction of CD40 ligand expression
L Ding1, J M Green, C B Thompson
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Insights
Strict regulation of CD40 ligand (CD40L) expression on T cells is crucial to prevent autoimmunity. This study reveals that while B7-1 is sufficient, other cellular interactions can also induce CD40L expression.
Area of Science:
- Immunology
- T cell biology
- Molecular immunology
Background:
- T cell-dependent antibody (Ab) responses rely on CD40 ligand (CD40L) interacting with CD40.
- Strict regulation of CD40L expression is vital to prevent B cell-mediated autoimmunity.
Purpose of the Study:
- To investigate the costimulatory signals required for CD40L induction on CD4+ T cells.
- To compare CD40L induction in normal and CD28-deficient mice.
Main Methods:
- Stimulation of CD4+ T cells from normal and CD28-deficient mice with anti-CD3, Con A, or peptide antigen.
- Assessment of CD40L expression using in vitro and in vivo models.
- Utilizing L cell transfectants as antigen-presenting cells (APCs).
Main Results:
- B7-1 expression was necessary and sufficient for CD40L induction on normal CD4+ T cells with L cell transfectants.
- Inhibition of B7/CD28 interactions only partially reduced CD40L induction with normal accessory cells.
- CD40L could be induced on CD4+ T cells from CD28-deficient mice.
Conclusions:
- Non-B7/CD28 cellular interactions can provide costimulatory signals for CD40L induction.
- The findings highlight alternative pathways for regulating CD40L expression in T cells.
Abstract:
The induction of a T cell-dependent Ab response is mediated by the interaction of the T cell activation Ag, CD40 ligand (CD40L), with CD40. Since this interaction is independent of Ag, coreceptors such as CD4, and MHC molecules, the expression of the CD40L must be strictly regulated or B cell-mediated autoimmunity may be produced. In this study, we examined the requirements for costimulatory signals for induction of CD40L expression in vitro and in vivo on CD4+ T cells from normal and CD28-deficient mice following stimulation with anti-CD3, Con A, or specific peptide Ag. Expression of B7-1 was both necessary and sufficient for induction of the CD40L on normal CD4+ T cells when L cell transfectants were used as APCs. When normal accessory cell populations were used, only partial inhibition of induction of the CD40L was observed with reagents that inhibit B7/CD28 interactions. Furthermore, the CD40L could be induced on CD4+ T cells from CD28-deficient mice. Thus, non-B7/CD28 cellular interactions can also mediate the costimulatory signals needed for induction of CD40L expression.