Autoantibodies against CD4 cells are associated with CD4 helper defects in
human immunodeficiency virus-infected patients
R Weimer, V Daniel, R Zimmermann, K Schimpf and G Opelz
Department of Transplantation Immunology, University of Heidelberg, FRG.
To investigate whether autoantibodies against CD4-positive lymphocytes
might induce helper dysfunction, autoantibody formation and T-cell function
was examined simultaneously in 61 hemophilia patients. Twenty patients were
human immunodeficiency virus (HIV)-negative, 26 HIV- positive stage CDC II
or III, and 15 were HIV-positive stage CDC IV. T lymphocytes, CD4-positive,
or CD8-positive T subsets were cocultured with B lymphocytes and pokeweed
mitogen (PWM) for 6 days and Ig- secreting cells were assessed in a reverse
hemolytic plaque assay. The presence of IgM, IgG, C3d, or gp120 on the
surface of T cells or T subsets was analyzed by flow cytometry.
Autoantibodies against CD4- positive T cells were not detected in controls
or HIV-negative patients, but were common in HIV-positive patients (20 of
41 patients). In patients with autoantibodies we found an increased
incidence of CD4 helper defects (P less than .0001 in CDC II or III
patients; P less than .02 in CDC IV patients). 12 of 13 patients with IgM
autoantibodies and 4 of 4 with IgG autoantibodies showed CD4 helper
defects. Complement fixation had no relevance. Autoantibody formation
against CD4 cells was not due to increased in vivo B-cell stimulation
(spontaneous plaque formation: 611 +/- 204 PFC/10(6) B cells in
autoantibody-negative patients v 650 +/- 202 PFC/10(6) B cells in
autoantibody-positive patients; not significant). Thus, our results suggest
that autoantibody formation is not caused by a general state of in vivo
B-cell activation. Rather, the production of autoantibodies appears to
coincide with defects in B-cell proliferation or differentiation, as shown
by reduced mitogen-stimulated B-cell responses in CDC II and III patients
(P less than .05). Autoantibodies against CD4 cells appear to be involved
in the pathogenesis of CD4 helper defects of HIV-infected patients.
Volume 77,
Issue 1,
pp. 133-140,
01/01/1991
Copyright © 1991 by The American Society of Hematology
