Impaired mononuclear cell tissue factor generation in patients with immunodeficiency diseases

Congenital immunodeficiency diseases are complex disorders of B- and T-cell function. We have studied monocyte-lymphocyte interaction in four patients with severe immunodeficiency disease using the coagulation protein, tissue factor, as a marker for monocyte activation. Phytohemagglutinin-induced tissue factor activity was markedly reduced in the cells from all four patients as compared to controls (p <0.02). Lipopolysaccharide-induced tissue factor activity, however, was abnormal in two patients with defects in stem cell differentiation (p <0.00001), but was normal in two patients with thymic hypofunction. Immune reconstitution of one patient with adenosine deaminase deficiency by bone marrow transplantation was marked by the return of mononuclear cell tissue factor activity to normal. Coculture experiments in three patients revealed suppression of tissue factor activity in two of the patients. Inhibitory activity gradually disappeared in the transplanted child as normal immune function was reconstituted. We conclude that mononuclear cell tissue factor activation is, in part, under immune control, in that T-cell function is required for optimal generation of activity, and immune reconstruction corrects the deficiency. Moreover, we have supplied further evidence for the interaction of blood coagulation with cell-mediated immunity by this demonstration of defective mononuclear cell tissue factor generation in children with immunodeficiency disease.