Soluble HLA Class I Molecules Exert Differentiated Influence on Renal Graft Condition

The function of soluble HLA (sHLA) antigens in the process of immunoregulation and especially in graft tolerance versus rejection has not yet been established. It has been suggested that donor-derived sHLA may exert an immunotolerant influence on the graft. We sought to determine the role of sHLA class I in kidney graft survival by evaluating the influence of these molecules on allotypic lymphocytotoxic antibodies and the concentration of gamma interferon (INF-γ). Analysis of sHLA was performed indirectly utilizing their ability to inhibit lymphocytotoxic reaction dependent on complement activation. To demonstrate the inhibitory properties of sHLA, we modified the NIH microcytotoxic test. Furthermore, we determined the concentration of INF-γ in all sera samples for comparison with the intensity of the cytotoxic test. The comparison of the intensity of cytotoxic test inhibition with the concentration of INF-γ revealed that high concentrations of this cytokine were associated with stronger inhibition of the cytotoxic test, thus with higher concentrations of sHLA class I molecules in recipient sera. We observed that high concentrations of sHLA class I molecules in recipient sera significantly inhibited cytotoxic reactions, which could contribute to a protective influence of sHLA on renal grafts. On the other hand, the observed increase of INF-γ concentration might be caused by sHLA themselves, which would produce a detrimental influence on a transplanted organ. Therefore we concluded that the role of sHLA class I molecules in renal graft condition remains ambiguous.