title: In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is dependent in part on the TNF family ligand 4-1BBL.
abstract: Immune complexes combining IL-2 with particular anti-IL-2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL-2 with anti-IL-2 (Clone S4B6) greatly enhances the biological potency of IL-2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL-2/anti-IL-2 mAb (IL-2/mAb) complexes induces 4-1BB expression on both adoptively transferred antigen-specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL-2/mAb-complex treatment was found to be dependent in part on the presence of 4-1BBL in the host. These effects were independent of IL-2-induced cell division, suggesting that 4-1BBL-induced survival signals contribute to IL-2/mAb-complex-induced T-cell accumulation in vivo.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gloria H Y
authors.initials: GH
authors.lastname: Lin
authors.forename: John C
authors.initials: JC
authors.lastname: Stone
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.forename: Tania H
authors.initials: TH
authors.lastname: Watts
mesh_terms: D053330:4-1BB Ligand / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9