Implantation of IL-2-containing osmotic pump prolongs the survival of superantigen-reactive T cells expanded in mice injected with bacterial superantigen.
In the present study we investigated the mechanism of deletion of superantigen (sAg)-reactive T cells expanded in sAg-injected mice. In staphylococcal enterotoxin A (SEA)-injected mice, IL-2 activity in serum peaked at 1 to 3 h and the expression of IL-2R alpha-chain (IL-2R alpha) on SEA-reactive (V beta 3+, or V beta 11+) T cells peaked at 6 to 12 h after the injection. Expansion of V beta 3+ or V beta 11+ T cells peaked at 2 days after the injection when most of these T cells were IL-2R alpha negative, and IL-2 activity was not detected at all in serum, suggesting the involvement of IL-2 deprivation in the deletion of expanded T cells. Implantation of an osmotic pump containing human rIL-2 (IL-2 pump) prolonged the expanded states of V beta 3+ or V beta 11+ T cells in SEA-injected C57BL/6 mice and of V beta 8+ T cells in SEB-injected MRL +/+ and Fas Ag-defective MRL-Ipr/Ipr mice. Adult thymectomy did not change at all the effect induced by implantation of IL-2 pump. DNA fragmentation was blocked substantially in mice co-treated with SEA and IL-2 pump. In addition, CD4+ T cell blasts, obtained by in vitro stimulation with rIL-2 of splenic CD4+ T cells from mice co-treated with SEA and IL-2 pump, produced substantial amounts of IL-2 upon restimulation with SEA. These results indicate that deprivation of IL-2 is deeply involved in the deletion of expanded sAg-reactive T cells and their anergy induction in sAg-injected mice.
Kuroda
K
K
Department of Microbiology and Immunology, Tokyo Women's Medical College, Japan.
Yagi
J
J
Imanishi
K
K
Yan
X J
XJ
Li
X Y
XY
Fujimaki
W
W
Kato
H
H
Miyoshi-Akiyama
T
T
Kumazawa
Y
Y
Abe
H
H
Uchiyama
T
T
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D017635:Clonal Anergy / Q000187:drug effects*; D017637:Clonal Deletion / Q000187:drug effects*; D004249:DNA Damage; D004768:Enterotoxins / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D015918:Infusion Pumps, Implantable; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013934:Thymectomy
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal