Induction of polyclonal CD8+ T cell activation and effector function by Pertussis toxin

Area of Science:

• Immunology
• Vaccinology

Background:

• Pertussis toxin (PTX) is known for its potent adjuvant activity, enhancing both innate and adaptive immunity.
• PTX's adjuvant effects on Th1/Th2 cells are largely attributed to CD80/86 costimulation by antigen-presenting cells (APCs).
• The impact of PTX on costimulatory and inhibitory molecule expression on T cells remained unclear.

Purpose of the Study:

• To investigate the effect of PTX on the expression of CD28, CTLA-4, and CD40L on CD4+ and CD8+ T cells.
• To elucidate the role of CD28-mediated signaling in PTX-induced T cell activation and cytokine production.

Main Methods:

• Spleen CD4+ and CD8+ T cells were incubated with PTX.
• Expression kinetics of CD28, CTLA-4, and CD40L were analyzed.
• Cytokine production (IFN-γ, Granzyme B, IL-17) and cell activation markers (CD69) were measured.
• Blocking antibodies against CD80/86 and CD28 were used to assess signaling pathways.

Main Results:

• PTX significantly upregulated CD28 expression on CD8+ T cells, but not on CD4+ T cells.
• CTLA-4 and CD40L expression remained largely unchanged on both T cell subsets.
• CD28 upregulation on CD8+ T cells correlated with increased CD69 expression, IFN-γ, Granzyme B, and IL-17 production.
• Anti-CD80/86 antibodies partially blocked PTX-induced CD8+ T cell activation and cytokine production.
• PTX treatment of purified CD8+ T cells increased CD28, CD69, and IFN-γ, an effect further enhanced by anti-CD28 antibodies.

Conclusions:

• PTX directly upregulates CD28 on CD8+ T cells, contributing to their activation and effector functions.
• CD80/86-mediated costimulation enhances PTX's direct effects on CD8+ T cells.
• These findings reveal a novel mechanism for PTX's adjuvant activity involving direct modulation of CD8+ T cell costimulatory molecule expression.