Mechanisms of inhibition of T cell IL-2 secretion by factor VIII concentrates.

We have continued our previous study of the inhibitory effects of factor VIII concentrates on IL-2 secretion by T cells. Experiments with an extended range of products confirm our previous conclusion that some but not all low, intermediate and high purity concentrates possess inhibitory activity on IL-2 secretion. The inhibition occurs almost immediately after addition of factor VIII concentrate and it was not possible to adsorb inhibitory activity with activated or non-activated cells; this suggests that the mechanism of inhibition involves interference with early T cell activation events rather than simple blocking of cell surface components by inhibitory molecules. The inhibitory components were shown to reside in different molecular weight fractions of concentrates. A strongly inhibitory component of approximately 200 kD and a minor species of approximately 60 kD were identified in strongly inhibitory concentrates. Some products contained a dialysable inhibitory substance which is most likely a salt as it was also present in some formulation buffers. The proportions of the inhibitory components varied widely between products. We have found that the pattern of inhibition using in vitro systems reflects that observed using a mouse in vivo antigen challenge method. In addition we have shown that the previously reported concentrate mediated inhibition of lectin induced low affinity IL-2 receptor (CD25) is mainly a consequence of diminished IL-2 secretion rather than a 'direct' effect on CD25 expression. Considering the wide variation between products of the same purity group, caution should be exercised in drawing conclusions concerning the immunosuppressive effects of a particular type of concentrate in haemophilia patients from study with only one product from that group.