The role of CD163L1 in CD8+ T cells

Principal Investigator: Brian Rudd

Co-PI: Andrew Grimson

Department of Microbiology and Immunology
Sponsor: NIH-National Institute of Allergy and Infectious Diseases (NIAID)
Grant Number: 1R21AI167858-01A1
Title: The role of CD163L1 in CD8+ T cells
Project Amount: $238,584
Project Period: November 2022 to October 2023

DESCRIPTION (provided by applicant): 

Following infection, naïve CD8+ T cells differentiate into effector or memory T cells, which help to eliminate pathogens and maintain long-term immunity. Despite decades of research, it is still not clear why some naïve CD8+ T cells become effectors and die, whereas others survive and become long-lived memory cells. The canonical model posits that a single lineage of CD8+ T cells undergoes phenotypic diversification after stimulation. However, our published work and preliminary data show that there are separate lineages of CD8+ T cells (fetal-derived and adult-derived) in the starting population, which are made during distinct windows of development and differentiate along different pathways during infection. This model suggests that the division of labor within the CD8+ T cell compartment is mediated by distinct ontogenetic lineages, similar to subpopulations of B cells (B1a, B1b, B2), which have unique functional capabilities. However, unlike the B cell field, the T cell field lacks a useful marker to identify fetal- and adult-derived CD8+ T cells in adult mice, and we still do not fully understand the underlying basis for their altered behavior. Based on our preliminary data and published findings, we have identified a scavenger receptor (CD163L1) that is specifically expressed on fetalderived CD8+ T cells and contributes to their more rapid innate-like functions. In Aim 1, we will establish whether CD163L1 is a marker for fetal-derived CD8+ T cells. In Aim 2, we will examine how CD163L1 alters the functions of CD8+ T cells. Our proposal is expected to open up new avenues of research and advance our conceptual understanding of the CD8+ T cell response to infection.