title: Differential Expression of Immune Checkpoint Modulators on In Vitro Primed CD4(+) and CD8(+) T Cells.
abstract: PD-1, TIM-3, and LAG-3 are molecules shown to have immune modulatory properties, and although initially classified as indicators of T cell hyporesponsiveness, it has become clear that they are also associated with the normal course of T cell activation. Functional studies have focused mainly on CD8(+) T cells during chronic inflammation due to interest in co-opting the cellular immune response to eliminate viral or cancerous threats; however, there remains a relative lack of data regarding the expression of these molecules on CD4(+) T cells. Here, we report that expression of the immune checkpoint (IC) molecules PD-1, LAG-3, and TIM-3 are differentially expressed on CD4(+) and CD8(+) T cells in the allogeneic response resulting from a mixed lymphocyte reaction. In these studies, PD-1 expression is higher on CD4(+) T cells compared to CD8(+) T cells. In contrast, TIM-3 is expressed at higher levels on CD8(+) T cells compared to CD4(+) T cells with an apparent reciprocity in that PD-1(+) CD4(+) T cells are frequently TIM-3(lo/-), while TIM-3-expressing CD8(+) T cells are largely PD-1(lo/-). In addition, there is a decrease in the frequency of TIM-3(+) CD4(+) cells producing IFN-γ and IL-5 compared to TIM-3(+) CD8(+) cells. Lastly, the memory T cell phenotype within each IC-expressing subset differs between CD4(+) and CD8(+) T cells. These findings highlight key differences in IC expression patterns between CD4(+) and CD8(+) T cells and may allow for more effective therapeutic targeting of these molecules in the future.
authors.affiliation: Biologics Research, Janssen R&D , Spring House, PA , USA.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Sabins
authors.affiliation: Biologics Research, Janssen R&D , Spring House, PA , USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Harman
authors.affiliation: Biologics Research, Janssen R&D , Spring House, PA , USA.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Barone
authors.affiliation: Biologics Research, Janssen R&D , Spring House, PA , USA.
authors.forename: Shixue
authors.initials: S
authors.lastname: Shen
authors.affiliation: Biologics Research, Janssen R&D , Spring House, PA , USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Santulli-Marotto
keywords: PD-1; T cells; TIM-3; immune checkpoint; in vitro