Polycytotoxic T Cells

Case 2016-676

UCLA researchers in the Department of Dermatology have characterized a novel subset of CD8+ T cells, termed polycytotoxic, that mediate killing of intracellular pathogens.

BACKGROUND

CD8+ T cells are known to engage in cytotoxic activity, where they use pore-forming proteins and proteases (granzyme B, granulysin, and perforin) to induce apoptosis in target cells. This cytotoxic role is activated in response to intracellular infections, but it could be suppressed to prevent Graft vs. Host disease, autoimmune disease, and other abnormal immune responses. However, not all CD8+ T cells express those cytotoxic proteins, and the specific population(s) responsible for antimicrobial defense have not previously been identified.

INNOVATION

Researchers at UCLA have identified a subset of CD8+ T cells called polycytotoxic T cells that express all the necessary cytotoxic proteins. By analyzing the surface expression, researchers also identified several biomarkers that can be used to purify this population of cells. Using in vitro functional testing, the polycytotoxic T cell subset was found to be more adept at killing intracellular pathogens.

APPLICATIONS

• Antibiotic development
• Vaccine target
• Cancer immunotherapy: biomarker for T cell target
• Organ transplantation: prevention of Graft vs. Host disease
• Autoimmune disease treatment
• Blockade of drug reactions: Stevens-Johnson syndrome, Toxic epiderman necrolysis, Drug-induced hypersensitivity syndrome (DIHS)

ADVANTAGES

• Polycytotoxic T cells show increased killing of intracellular pathogens
• Identified a subpopulation of T cells that expresses the necessary cytotoxic proteins- can activate or repress this population specifically, depending on context

RELATED MATERIALS

Busch, M. et al. (2016). Lipoarabinomannan-responsive polycytotoxic T cells are associated with protection in human tuberculosis. Am J Respir Crit Care Med.