The selective ablation of interleukin 2-producing cells isolated from transgenic mice.
To better understand the requirement for interleukin 2 (IL-2) in specific immune responses, we have established the use of cell ablation to selectively eliminate T cells that produce IL-2. To accomplish this we have generated transgenic mice that express the herpes simplex virus 1-thymidine kinase (HSV-TK) gene under the transcriptional control of the murine IL-2 promoter that renders IL-2-producing cells sensitive to the cytotoxic effects of the antiviral drug ganciclovir (GANC). HSV-TK activity was specifically expressed in activated T cells from transgenic mice. When CD4 T cells from transgenic mice were stimulated with the superantigen staphylococcal enterotoxin A (SEA) in the presence of GANC, proliferation and IL-2 production were almost completely inhibited and the activated CD4+V beta 3+ T cell population, eliminated. Proliferation was not restored by adding IL-2, showing that most proliferating cells are not bystander cells. In contrast, the proliferative response to concanavalin A (Con A) was only partially inhibited by treatment of CD4 T cells with GANC, although the efficiency of eliminating IL-2-producing cells was shown to be comparable with that achieved using SEA. This suggests that a portion of the proliferative response to Con A occurs via an alternative pathway not requiring IL-2 synthesis and release.
Minasi
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LE
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
Kamogawa
Y
Y
Carding
S
S
Bottomly
K
K
Flavell
R A
RA
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D003208:Concanavalin A / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018139:Simplexvirus / Q000201:enzymology; D013154:Spleen / Q000166:cytology / Q000201:enzymology; D013211:Staphylococcus aureus / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D017186:Titrimetry
D004768:Enterotoxins; D007376:Interleukin-2; D003208:Concanavalin A; C026066:enterotoxin A, Staphylococcal; D013937:Thymidine Kinase; D015774:Ganciclovir