Table 2.
Effects of belatacept and tacrolimus in vitro on donor antigen-activated follicular T-helper (Tfh) and B-cells.
| Immunological reaction | Defined by | Effect by belatacept in vitro | Effect by tacrolimus in vitro | Comparison belatacept vs. tacrolimusa |
|---|---|---|---|---|
| Tfh-cell generation | CXCR5 expression ↑ on CD4+ T-cells | Inhibition (minimal) | Inhibition (minimal) | bela = tac |
| Tfh-cell activation | PD-1 expression ↑ on CD4+CXCR5+ T-cells | Inhibition (partial) | Inhibition (partial) | bela = tac |
| Activated Tfh-cell generation | CXCR5+PD-1+ double expression ↑ on CD4+ T-cells | Inhibition (partial) | Inhibition (partial) | bela = tac |
| IL-21+-activated Tfh-cell generation | The proportion of IL-21+ CXCR5+PD-1+ ↑ within CD4+ T-cells | Inhibition (partial) | Inhibition (partial) | bela = tac |
| IL-21 production by activated Tfh-cells | Intracellular IL-21 expression of CXCR5+PD-1+ CD4+ T-cells | None | Inhibition (minimal) | bela = tac |
| B-cell activation | CD86 expression ↑ on B-cells | Inhibition (partial) | Inhibition (partial) | bela is more efficient than tacb |
| Transitional B-cell survival | The proportion of CD24+CD38++ B-cells | None | Inhibition (partial) | bela is more benificial than tacc |
| Plasmablast formation | Proportion of B-cells differentiated into CD27+CD38++ B-cells | In PBMCs: none | In PBMCs: inhibition (partial) | bela is less efficient than tacd |
| In isolated system with Tfh- and B-cells: inhibition (almost completely) | In isolated system with Tfh- and B-cells: inhibition (completely) | bela is slightly less efficient than tac | ||
| IgM production | Total IgM in supernatant of cocultures | In PBMCs: inhibition (partial) | In PBMCs: inhibition (partial) | bela = tac |
| In isolated system with Tfh- and B-cells: inhibition (almost completely) | In isolated system with Tfh- and B-cells: inhibition (completely) | bela is slightly less efficient than tac |
bela, belatacept; IgM, immunoglobulin M; PBMCs, peripheral blood mononuclear cells; tac, tacrolimus.
aComparison of the relative inhibition by belatacept in vitro and tacrolimus in vitro.
bThese observations were confirmed in a multivariable regression analysis for memory B-cells, but not for naïve B-cells (Table 1).
cThese observations were not confirmed in a multivariable regression analysis (Table 1).
dThese observations were confirmed in a multivariable regression analysis (Table 1).