CD8+ lymphocyte decrease in HIV disease: association with anti-CD4+ but not with anti-CD8+ lymphocyte autoantibodies.
HIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti-CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti-CD4+ and anti-CD8+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti-CD8+ lymphocyte autoantibodies were found more often in HIV + hemophilia patients (75/105 = 71%) than HIV- hemophilia patients (13/37 = 35%; p < 0.0001), patients with pharyngeal carcinoma (20/44 = 45%; P = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93-223 = 42%; p < 0.0001). Anti-CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti-CD4+ antibodies in healthy controls (p < 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV- patients (p = 0.01). In HIV+ patients, however, anti-CD4+ autoantibodies were found more often than anti-CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti-CD4+ (p = 0.01) but not with anti-CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti-CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.
Daniel
V
V
Department of Transplantation Immunology, University of Heidelberg, Germany.
Süsal
C
C
Weimer
R
R
Zipperle
S
S
Kröpelin
M
M
Zimmermann
R
R
Huth-Kühne
A
A
Gerhard
I
I
Maier
H
H
Opelz
G
G
D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015933:Complement C3d / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000097:blood; D006679:HIV Seropositivity / Q000276:immunology*; D006467:Hemophilia A / Q000150:complications; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018655:Lymphocyte Count
D001323:Autoantibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015933:Complement C3d