Increased cell surface free thiols identify effector CD8+ T cells undergoing T cell receptor stimulation

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• T cell receptor (TCR) recognition of peptide-MHC complexes triggers reactive oxygen intermediate (ROI) production in CD8(+) T cells.
• The membrane permeability of ROI necessitates protective mechanisms against surface protein overoxidation.

Purpose of the Study:

• To investigate the role of cell surface free thiols (CSFT) in CD8(+) T cells during immune responses.
• To determine how CSFT levels change during T cell development, activation, differentiation, and in response to infection.

Main Methods:

• Utilized fluorescently labeled maleimide conjugates to quantify CSFT levels.
• Analyzed CSFT levels in CD8(+) T cells across various developmental stages, activation states, and during viral infections (acute and chronic).
• Compared CSFT levels between lymphoid and non-lymphoid organs and between effector and memory T cells.

Main Results:

• CSFT levels were higher in CD8(+) single positive (SP) T cells during development.
• CSFT levels increased upon activation, prior to division, and continued to rise during proliferation.
• Antigen-specific effector CD8(+) T cells exhibited elevated CSFT during acute and chronic viral infections, particularly in lymphoid organs.
• Elevated CSFT levels on effector CD8(+) T cells correlated with ongoing T cell receptor stimulation.

Conclusions:

• CD8(+) T cells upregulate CSFT in response to TCR ligation and ROI production.
• CSFT upregulation serves as a protective mechanism against surface protein overoxidation following immune stimulation.
• CSFT levels can serve as an indicator of active TCR stimulation in effector CD8(+) T cells during infection.