B-cell activation during HIV-1 infection. III. Down-regulating effect of mitogens.
Spontaneous in vitro production of HIV-1-specific antibodies, a hallmark of infected subjects, is often down-regulated by the addition of pokeweed mitogen. We observed that a decrease in such ongoing anti-HIV-1 antibody synthesis could also be induced in cultures from most patients by addition of phytohemagglutinin and Concanavalin A, but not by Epstein-Barr virus, a selective B-cell mitogen. In most cases, this down-regulatory effect of mitogens was evident within the first 24 h of culture. The observed mitogen-associated decrease in spontaneous antibody synthesis was prevented by treating peripheral blood mononuclear cells with agents inhibiting non-major histocompatibility complex-restricted cytotoxic activity or by adding third-party cells to the cultures. In most cases, the mitogen-induced effect was also counteracted by removal of T lymphocytes or CD8+ T-cell sub-population. These findings recall a similar phenomenon observed in normal subjects following intentional immunization, and indicate that mitogen-induced down-regulation of spontaneous in vitro anti-HIV-1-antibody production most probably occurs through a lectin-dependent cytotoxic effect on activated B cells.
Amadori
A
A
Institute of Oncology, Interuniversity Center for Research on Cancer, University of Padua, Italy.
Zamarchi
R
R
Veronese
M L
ML
Panozzo
M
M
Mazza
M R
MR
Barelli
A
A
Borri
A
A
Chieco-Bianchi
L
L
D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens; D002469:Cell Separation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008213:Lymphocyte Activation; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015483:HIV Antibodies; D007136:Immunoglobulins; D011043:Pokeweed Mitogens; C030365:leucine methyl ester; D007930:Leucine