B7-H1 Receptor Induced T-Helper Cell Differentiation in vitro

Objectives: Differentiation of T helper (Th) cells into the major subtypes of Th effector cells (Th1, Th2, Th17, Treg) is induced by combined signals. In cell-mediated immune response the B7-H1 receptor has important regulatory functions. Expression of B7-H1promotes the development of regulatory T cells (Treg), which actively suppress Th effector cells. Porphyromonas gingivalis (P. gingivalis), a putative periodontal pathogen, previously has been shown to induce B7-H1 in oral squamous carcinoma cells (SCC-25). The aim of this study was to investigate the differentiation of naïve Th cells after co-cultivation with B7-H1 expressing SCC-25 cells.

Methods: SCC-25 cells were induced to express B7-H1 by infection with P. gingivalis (W83). Non-infected and infected cells treated with B7-H1 blocking-antibodies were used as negative controls. Separated naïve Th cells were co-cultivated with the SCC-25 cells. After one week, the cells were immuno-stained for the Th phenotype and analyzed by flow-cytometry.

Results: After co-cultivation 9% (±5) (non-infected cells) and 36% (±9) (infected cells) of the Th cells showed Treg phenotype (p< 0.05). Treatment of the infected cells with a B7-H1 blocking-antibody reduced the Treg number to 12% (±8) while usage of isotype controls induced 31% (±7) Treg (p< 0.05). The Th1 phenotype was demonstrated to 17% (±9) (non-infected) and 15% (±18) (infected) while 4% (±5) (non-infected) and 9% (±10) (infected) T cells showed Th2 markers. Th17 cells were induced to 19% (± 8) co-cultivated with non-infected cells and to 38% (±6) with infected cells.

Conclusions:  Co-cultivation of naïve T helper cells with oral B7-H1 expressing epithelial cells promotes differentiation of a T cell phenotype that is able to suppress Th effector cells.