title: HLA-Dr-expressing CD8bright cells are only temporarily present in the circulation during subcutaneous recombinant interleukin-2 therapy in renal cell carcinoma patients.
abstract: The effect of subcutaneous recombinant interleukin-2 (rIL-2) therapy on the "activation status" of peripheral blood lymphocytes (PBL) of 17 renal cell carcinoma patients was investigated in a longitudinal study. The expression of the activation markers HLA-Dr and CD25 on cytotoxic T cells, helper T cells, and natural killer (NK) cells, was analysed using two-colour flow cytometry of whole-blood samples. In addition, the ability of isolated PBL to proliferate in vitro in response to various stimuli was investigated. The absolute amounts of NK cells and HLA-DR-expressing NK cells increased continuously during the whole course of therapy. The absolute amounts of T cells and HLA-Dr-expressing T cells, however, showed an early increase only during the first 1 or 2 weeks of therapy, after which the absolute amounts of HLA-Dr-expressing T cells decreased. In particular, the absolute amount of HLA-Dr-expressing CD8bright+ T cells was significantly lowered in the second half of therapy. PBL collected on day 7 of therapy (post-cycle-1 PBL) showed, as compared to those collected prior to therapy (pretherapy PBL), a decreased proliferative response in vitro after stimulation with phytohaemagglutinin, concanavalin A, soluble CD3 mAb (WT32) or rIL-2. This decreased in vitro response of post-cycle-1 PBL was also reflected in a decrease in the percentage of CD8bright+ T cells expressing HLA-Dr in cultures with rIL-2 or CD3 mAb, in contrast to cultures of pretherapy PBL, which showed an increase of this percentage. We conclude that T cells are the predominantly stimulated subpopulation during the first 2 weeks of subcutaneous rIL-2 therapy. The significant decrease in the absolute amounts of HLA-Dr-expressing T cells in the peripheral blood during the second half of therapy may partly be explained by a decreased responsiveness to rIL-2, but a selective redistribution of HLA-Dr-expressing cells may also be involved.
authors.affiliation: Department of Clinical Immunology, Internal Medicine, University Hospital Groningen, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Janssen
authors.forename: J
authors.initials: J
authors.lastname: Buter
authors.forename: E
authors.initials: E
authors.lastname: Straatsma
authors.forename: A A
authors.initials: AA
authors.lastname: Heijn
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
authors.forename: T H
authors.initials: TH
authors.lastname: The
authors.forename: L
authors.initials: L
authors.lastname: de Leij
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins