title: Modulation by IL-2 of CD70 and CD27 expression on CD8+ T cells: importance for the therapeutic effectiveness of cell transfer immunotherapy.
abstract: Proper T cell function relies on the integration of signals delivered by Ag, cytokine, and costimulatory receptors. In this study, the interactions between IL-2, CD27, and its ligand CD70 and their effects on human T cell function were examined. Unstimulated CD8(+) T cells expressed relatively low levels of CD70 and high levels of CD27. Incubation in vitro with high doses of IL-2 (3,000 IU/ml) or administration of IL-2 in vivo resulted in substantial up-regulation of CD70 expression and the concomitant loss of cell surface CD27 expression on CD8(+) cells. Withdrawal of IL-2 from activated CD8(+) T cells that had been maintained in IL-2 resulted in a reversal of the expression of these two markers, whereas reciprocal changes were seen following treatment of PBMCs with IL-2. The proliferation observed in cells stimulated with IL-2 primarily occurred in a subset of the CD70(+)CD8(+) T cells that up-regulated IL-2 receptor expression but did not occur in CD70(-)CD8(+) T cells. Blocking CD70 resulted in a significant reduction of T cell proliferation induced by high-dose IL-2, indicating that the interaction of CD70 with CD27 played a direct role in T cell activation mediated by IL-2. Finally, studies conducted on tumor-infiltrating lymphocyte (TIL) samples that were administered to melanoma patients indicated that the size of the pool of CD27(+)CD8(+) T cells in bulk TILs was highly associated (p = 0.004) with the ability of these TILs to mediate tumor regression following adoptive transfer.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Huang
authors.forename: Keith W
authors.initials: KW
authors.lastname: Kerstann
authors.forename: Mojgan
authors.initials: M
authors.lastname: Ahmadzadeh
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053282:CD27 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D007376:Interleukin-2; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors