Current approaches to evaluate the function of cytotoxic T-cells in non-human primates

Abstract

Cytotoxic T-lymphocytes (CTL) are a subset of T-cells that play a critical role in protecting against intracellular infections and cancer, and have the ability to identify and kill infected or transformed cells expressing non-self peptides associated with major histocompatibility (MHC) Class I molecules. Conversely, aberrant CTL activity can contribute to immune-related pathology under conditions of overwhelming infection or autoimmunity. Disease-modifying therapeutics can have unintended effects on CTL, and a growing number of therapeutics are intended to either suppress or enhance CTL or their functions. The susceptibility of CTL to unintended effects from common therapeutic modalities underscores the need for a better understanding of the impact that such therapies have on CTL function and the associated safety implications. While there are reliable ways of quantifying CTL, notably via flow cytometric analysis of specific CTL markers, it has been a greater challenge to implement fit-for-purpose methods measuring CTL function in the context of safety studies of therapeutics. This review focuses on methods for measuring CTL responses in the context of drug safety and pharmacology testing, with the goals of informing the reader about current approaches, evaluating their pros and cons, and providing perspectives on the utility of these approaches for safety evaluation.

Keywords:

• Cytotoxic T-cells
• lymphocytes
• flow cytometry
• intracellular cytokine staining
• ELISpot
• cytokine
• tetramer
• viral vector
• adenovirus vaccine
• cytotoxicity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Acknowledgements

The authors would like to thank Members of the Health and Environmental Sciences Institute (HESI) Immuno-Safety Technical Committee and members of the Methods Development Working group. The authors would also like to extend a word of thanks to former project manager Dr. Stan Parish

Additional information

Funding

This HESI scientific initiative is primarily supported by the in-kind contributions (from public and private sector participants) of time, expertise, and experimental and/or development effort. These contributions are supplemented by direct funding (that primarily supports program infrastructure and management and some project-related direct expenses) provided by HESI's corporate sponsors. A list of supporting organizations (public and private) is available at http://hesiglobal.org. HESI is a nonprofit scientific organization that facilitates public and private partnerships in human and environmental health. The Immunosafety Technical committee is committed to advancing the scientific understanding of issues related to immune safety and translation to human health risk assessment.