Effects of 3'-azido-3'-deoxythymidine (AZT) on short-term cultured human peripheral blood lymphocytes.
Although an optimal dose-regimen has still not been established, the antiviral drug 3'-azido-3'-deoxythymidine is known to improve the clinical condition of patients suffering from acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. The drug effect has mainly been assessed in terms of survival time and/or immunological parameters. One of the most prominent immunological features associated with immunodeficiency virus infection is a persistant hypergammaglobulinaemia due to in vivo polyclonal B-lymphocyte activation. In vitro this is reflected by a hyporesponsiveness of peripheral blood B-lymphocytes to mitogen and antigen induced activation. The present paper deals with the in vitro impact of 3'-azido-3'-deoxythymidine on the immunoglobulin secretion in short-term cultures of peripheral blood lymphocytes. Twenty-four human immunodeficiency virus antibody positive (seropositive) and 24 antibody negative (seronegative) individuals were studied. In addition, T- and B-cell proliferation and the distribution of cell surface markers were determined in 3'-azido-3'-deoxythymidine-supplemented cultures of peripheral blood lymphocytes from eight seronegative subjects. At concentrations similar to those reported in clinical trials, 3'-azido-3'-deoxythymidine was found to suppress the mitogen and antigen induced proliferation of T-cells from seronegative subjects. In contrast, B-cell proliferation and the distribution of membrane markers appeared to be unaffected by the drug. Furthermore, 3'-azido-3'-deoxythymidine did not alter the in vivo immunoglobulin secretion capacity in autologous or allogeneic cultures of lymphocytes from seropositive subjects. In human immunodeficiency virus-infected individuals the number of unactivated, circulating B-cells is significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Tauris
P
P
University Department of Clinical Immunology, University of Arhus, Denmark.
Møller
B
B
Petersen
C M
CM
Black
F T
FT
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000494:pharmacology*
D007136:Immunoglobulins; D015215:Zidovudine; D004247:DNA