Increased T-cell colony formation in AIDS patients treated with zidovudine: a possible mechanism for increased lymphocyte number.
Treatment of AIDS patients with zidovudine is associated with an increase in lymphocyte counts. The mechanism for this increase is unclear and somewhat surprising in view of the myelosuppressive effect of zidovudine. To investigate this further, we measured lymphocyte numbers, T-cell subsets, and the ability of peripheral blood mononuclear cells (PBMC) to form T-cell colonies (T-CFC) in agar formation, in a group of patients with AIDS, before and during the first 6 months of zidovudine treatment. Eight patients were treated for an average of 11 weeks. There was a significant increase in T-CFC with zidovudine treatment (11.5 +/- 4.7% versus 29.8 +/- 6.9%, P less than 0.02 using a paired Student's t-test). There was a non-significant trend in the improvement of lymphocyte counts in these patients (872 +/- 117 versus 1102 +/- 204, NS). In vitro exposure of lymphocytes to zidovudine (200 mumol/l) resulted in modest suppression of T-CFC formation, suggesting that the effect of zidovudine treatment is indirect. Given that we have previously shown that inactivated HIV can inhibit T-CFC formation, we suggest that zidovudine treatment indirectly allows an increase in lymphocyte number by decreasing virus load, thereby permitting greater T-cell repopulation.
Levy
E M
EM
Department of Microbiology, Boston University School of Medicine, Massachusetts.
Wu
J M
JM
Cohn
S E
SE
Liebman
H
H
Black
P H
PH
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D003114:Colony-Forming Units Assay; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D015215:Zidovudine / Q000627:therapeutic use*
D015215:Zidovudine