Zidovudine (azido dideoxythymidine) inhibits characteristic early alterations of lymphoid cell populations in retrovirus-induced murine AIDS.
Using flow cytometry technology and multiparameter analyses, we report early and characteristic alterations in lymphoid cell profile in spleen and lymph nodes due to LP-BM5 retrovirus disease (murine AIDS (MAIDS)) and the effect of azido dideoxythymidine, a nucleoside inhibitor, on these changes. MAIDS has been characterized by rapid and profound lymphoproliferation accompanied by hypergammaglobulinemia and immunosuppression. As early as 2 wk postinfection, there is a selective depletion of CD8+ cells whereas the total number of CD4+ cells increases throughout the first 8 wk of infection although the frequency is relatively stable. These population changes were partially delayed by oral AZT therapy for 6 wk postinfection. Ly-6C (AL-21) is expressed on roughly 50% of CD4+ and CD8+ cells in C57BL/6 mice. In MAIDS, the residual population of CD8+ cells is primarily Ly-6C+. The CD4+ cells have a transient increase in ratio of Ly-6C+/Ly-6C- cells at 2 wk postinfection but by 6 wk are primarily Ly-6C-. There was an increase in both the total number and percentage of Mac 1+ cells and a selective depletion of certain splenic B cell subpopulations. Azido dideoxythymidine delays these early population changes.
Portnoi
D
D
Department of Genetics, Stanford University School of Medicine, CA 94305.
Stall
A M
AM
Schwartz
D
D
Merigan
T C
TC
Herzenberg
L A
LA
Basham
T
T
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D016177:Macrophage-1 Antigen; D051379:Mice; D008807:Mice, Inbred BALB C; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology; D015215:Zidovudine / Q000494:pharmacology*
D000943:Antigens, Differentiation; D000950:Antigens, Ly; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D015215:Zidovudine