Antigen-specific CD8 T cells in cell cycle circulate in the blood after vaccination

Area of Science:

• Immunology
• Cell Biology
• Vaccinology

Background:

• Clonal expansion of antigen-specific T cells is fundamental to adaptive immunity.
• The precise locations where T cells initiate and complete cell division remain largely unknown.
• Limited experimental methods have hindered the study of T cell cycle progression in vivo.

Purpose of the Study:

• To investigate the cell cycle status of antigen-specific CD8 T cells following vaccination.
• To identify the anatomical sites where T cell proliferation occurs after viral vector immunization.
• To develop and apply novel flow cytometry techniques for analyzing T cell cycle phases.

Main Methods:

• Utilized Ki67 and DNA staining in conjunction with a new flow cytometry analysis strategy.
• Administered intramuscular vaccination with antigen-expressing viral vectors to BALB/c mice.
• Quantified antigen-specific CD8 T cells in G0, G1, and S-G2/M phases of the cell cycle.

Main Results:

• Antigen-specific CD8 T cells in the S-G2/M proliferative phases were detected early post-vaccination.
• Proliferating cells were found in lymph nodes, spleen, and unexpectedly, in the peripheral blood.
• A significant population of proliferating cells exhibited high scatter, previously undetected, underestimating cell frequency by up to sixfold in lymph nodes.

Conclusions:

• The blood serves as a site for the proliferation of antigen-specific CD8 T cells following vaccination.
• Current analytical methods may significantly underestimate the frequency of antigen-specific T cells.
• The presence of cycling T cells in blood offers novel translational opportunities for immunotherapy and vaccine development.