Preferential T cell expansion by artificial antigen presenting cells expressing 4-1BBL alone or in combination with CD80 or CD86.

Abstract

Varieties of artificial antigen presenting cells (aAPCs) with different efficiencies have been introduced to expand whole T cell population or antigen specific ones for the purpose of T cell therapy. From antibody coated beads to gene modified dendritic cells each has some advantages and disadvantages. However, no one can ignore the importance and the necessity of costimulation interaction during T cell activation. This study was designed to compare the effectiveness of CD80/CD86 and 4-1BBL, two major costimulatory families, in costimulation of autologous T cell responses. We used recombinant non-replicative adenoviral vectors and transferred genes of these ligands to autologous blood monocytes and skin fibroblasts to create aAPCs system. T cell response to anti-CD3 pan stimulation and some viral peptide Ags, in co-culture with gene modified monocytes and fibroblasts were studied using CFSE and HLA tetramers, respectively. Over-expression of ligands was able to expand the T cell population significantly higher than normal cells with no interference with antigen stimulation. Presence of 4-1BBL alone or in combination with B7 members enhanced T cell expansion and promoted more Ag-specific cells to accumulate in these culture systems. Considering the inhibitory proportion of B7 costimulation route, 4-1BBL, as an alternative signaling pathway, in combination with B7 will promote T cell proliferation and expansion.