Immunomodulatory effect of zidovudine (ZDV) on cytotoxic T lymphocytes previously exposed to ZDV.
In a previous study, zidovudine (ZDV) was shown to cause a concentration-dependent inhibition of antigen-specific cytotoxic T-lymphocyte (CTL) clonal expansion (S. Francke, C. G. Orosz, K. A. Hayes, and L. E. Mathes, Antimicrob. Agents Chemother. 44:1900-1905, 2000). However, this suppressive effect was lost if exposure to ZDV was delayed for 24 to 48 h during the antigen sensitization period, suggesting that antigen-primed CTL may be less susceptible than naive T lymphocytes to the suppressive effects of ZDV. The present study was undertaken to determine if naive T lymphocytes were more sensitive to the suppressive effects of ZDV than T lymphocytes previously exposed to antigen. The 50% inhibitory concentration (IC(50)) values of ZDV were determined on naive and antigen-primed T-cell responses in an alloantigen system. Lymphocyte cultures with continuous antigen exposure (double prime) were more resistant to ZDV suppression (IC(50) = 316 micro M) than were naive lymphocytes (IC(50) = 87.5 micro M). Interestingly, lymphocytes that were antigen primed but deprived of antigen during the final 7 days of culture (prime/hold) were exquisitely sensitive to ZDV suppression (IC(50) = 29.3 micro M). The addition of 80 micro M ZDV during the initial priming of the single-prime (prime/hold) and double-prime cultures did not select for a more drug-resistant cell population. The differences in ZDV sensitivities are likely a reflection of the physiological properties of the lymphocytes related to their activation state.
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Sabine
S
Francke
Charles G
CG
Orosz
Jason
J
Hsu
Lawrence E
LE
Mathes
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000956:Antigens, Viral / Q000276:immunology; D002469:Cell Separation; D002860:Chromium Radioisotopes; D024882:Drug Resistance, Viral; D005260:Female; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D015215:Zidovudine / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D000956:Antigens, Viral; D002860:Chromium Radioisotopes; D007376:Interleukin-2; D015215:Zidovudine