Fig. 4

Induced proliferations of T cell subsets and coexpression of costimulatory and coinhibitory receptors (immune checkpoint molecules). Differences in short term (3 day) or long term (7 day) T cell cultures undergoing stimulations with varlilumab or control antibody (hIgG) show more CD8+ cells (a) entering the division cycle in the varlilumab-treated group. Numbers in the histograms refer to the percent of indicated cells (CD8+ or CD3+CD8-) that are dividing as reflected by CFSE staining (a bottom panel). b CD27+ proliferating CD4+ and CD8+ T cells were stained with antibodies to additional cell surface markers representing costimulatory (GITR, OX40, ICOS and 4-1BB) and coinhibitory (PD-1) molecules. Dividing CD8+ and CD4+ T cells show marked upregulation of costimulatory and coinhibitory molecules relative to non-dividing cells. Shaded histograms represent T cells stimulated with control antibody and anti-CD3 (OKT3). Numbers in the histograms refer to percent of T cells (dividing or non-dividing CD8 or CD4 cells) that are positive for the indicated costimulatory or coinhibitory marker (b)