Lymphocyte dysfunction in chronic graft-versus-host disease
A Saxon, RE McIntyre, RH Stevens and RP Gale
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.
Volume 58,
Issue 4,
pp. 746-751,
10/01/1981
Copyright © 1981 by The American Society of Hematology
