Lymphocyte dysfunction in chronic graft-versus-host disease

Abstract

Three recipients of HLA-identical bone marrow transplants developed chronic graft-versus-host disease (cGVHD) and hypergammaglobulinemia. All three had evidence of abnormal B-lymphocyte function, including a polyclonal increase in immunoglobulins (Ig), antinuclear antibodies, rheumatoid factor, lymphocytotoxins, and increased immune complexes. T-lymphocyte function was also abnormal, including decreased mitogen reactivity and delayed cutaneous hypersensitivity. The cellular basis of these immune abnormalities was studied in an in vitro system in which we analyzed spontaneous pokeweed mitogen (PWM) driven Ig synthesis. Multiple defects in both T- and B-lymphocyte function were detected. In contrast to normal B cells, circulating B cells from all three patients with cGVHD spontaneously synthesized in vitro greater than 200 ng of IgG and in two of the three greater than 175 ng of IgM. This increase in spontaneous Ig synthesis was not due to a deficiency of regulatory cells, since T cells from the three patients suppressed spontaneous Ig synthesis in a normal fashion. In contrast to this increased spontaneous Ig synthesis, the response of the patients' B cells to PWM-driven Ig synthesis was normal. Using the PWM system we demonstrated several defects in these patients' T cells, including increased suppressor activity and decreased helper cell activity. These data indicate that some patients with cGVHD have multiple defects in both T- and B-cell function that may contribute to their profound immune deficiency.