Canine CD4(+)CD8(+) double-positive T cells can develop from CD4(+) and CD8(+) T cells

Area of Science:

• Immunology
• Veterinary Immunology
• T cell biology

Background:

• Traditionally, CD4 and CD8 T cell receptor expression was considered mutually exclusive.
• Mature CD4(+)CD8(+) double-positive (dp) T cells, exhibiting activated phenotypes, have been identified in canine peripheral blood.
• Canine CD4(+)CD8(+)dp T cells are heterogeneous, classified by CD4 and CD8α expression intensity.

Purpose of the Study:

• To investigate the progenitor cells responsible for generating canine CD4(+)CD8(+)dp T cells.
• To elucidate the differentiation pathways of canine dp T cells.

Main Methods:

• Cell tracing experiments were employed to identify T cell progenitors.
• In vitro stimulation assays using purified T cell populations (CD4(+)sp, CD8α(+)sp, CD4(-)CD8α(-)dn) were performed.
• Analysis of CD4 and CD8α expression and mRNA synthesis was conducted.

Main Results:

• Both CD4(+) single-positive (sp) and CD8α(+)sp T cells were identified as progenitors of canine CD4(+)CD8(+)dp T cells following in vitro stimulation.
• CD4(+)sp T cells primarily upregulate CD8αα, while CD8α(+)sp T cells can gain CD4 expression, particularly in the presence of CD4(+)sp cells or their secreted factors.
• De novo synthesis, not trogocytosis, is the likely mechanism for CD4 upregulation on CD8α(+)sp T cells.
• CD4(+)sp T cells are more potent progenitors of CD4(+)CD8α(+)dp T cells than CD8α(+)sp T cells.

Conclusions:

• Canine CD4(+)sp T cells are the predominant progenitors of CD4(+)CD8α(+)dp T cells.
• The differentiation of CD8α(+)sp T cells into dp T cells is dependent on co-stimulation or factors from CD4(+)sp T cells.
• Upregulation of CD4 on CD8α(+)sp T cells occurs via de novo synthesis, indicating a distinct differentiation pathway.