B cells expressing IL-10 mRNA modulate memory T cells after DNA-Hsp65 immunization

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• DNA vaccines utilize plasmids to induce long-term protein production in eukaryotic cells.
• Previous studies demonstrated that DNA vaccination with pcDNA3-Hsp65 confers protection against Mycobacterium tuberculosis.
• Memory T cells are crucial for protective immunity following vaccination.

Purpose of the Study:

• To investigate the mechanisms by which B cells influence memory T-cell development after DNA vaccination with pcDNA3-Hsp65.
• To elucidate the role of B cells in modulating the immune response to DNA immunization.

Main Methods:

• Mice (C57BL/6 and BKO) received multiple immunizations with naked pcDNA-Hsp65.
• Flow cytometry was used to quantify effector memory T cells (TEM) and memory CD8+ T cells.
• Real-time quantitative polymerase chain reaction (qPCR) assessed cytokine mRNA levels (interferon-gamma, IL-12, IL-10) in spleen cells and purified B cells.

Main Results:

• A specific B-cell subpopulation expressing IL-10 was identified.
• This IL-10-producing B cell subpopulation downregulated pro-inflammatory cytokine expression in the spleen.
• The observed downregulation led to increased survival of CD4+ TEM and CD8+ TEM/CD127+ cells.

Conclusions:

• B cells play a significant role in modulating T-cell memory responses after DNA immunization.
• IL-10 produced by a subset of B cells is a key mediator in this process.
• Understanding these B-cell mechanisms can inform the development of more effective DNA vaccines.