Adoptive immunotherapy with interleukin-2 (IL-2) results in diminished IL-2 production by stimulated peripheral blood lymphocytes.
We examined the responses of peripheral blood lymphocytes (PBL) to a panel of T-cell mitogens in patients receiving adoptive transfers of tumor-infiltrating lymphocytes and continuous infusions of interleukin-2 (IL-2) for treatment of advanced cancer. All patients showed diminished proliferative responses to soluble and alloantigens, lectins, anti-CD3, and IL-2 during therapy. The non-major histocompatibility complex (MHC)-restricted cytolytic activities of PBL were increased by treatment and were further augmented by IL-2 in vitro. The expression of approximately 55-kd low-affinity IL-2 receptors (IL-2R) by PBL increased during treatment but functional IL-2R were simultaneously down-regulated. Proliferative responses were partially restored to pretreatment levels when PBL were costimulated with recombinant IL-2 and mitogens. Lectin stimulation of PBL produced little IL-2 secretion during treatment, while IFN-gamma secretion persisted. We conclude that infusions of IL-2 down-regulate the expression of functional IL-2R, decrease the secretion of IL-2, and lead to decreased mitogen responses by PBL.
Kradin
R
R
Department of Medicine, Massachusetts General Hospital, Boston 02114.
Kurnick
J
J
Gifford
J
J
Pinto
C
C
Preffer
F
F
Lazarus
D
D
D000954:Antigens, Surface / Q000276:immunology; D003131:Combined Modality Therapy; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D008175:Lung Neoplasms / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000628:therapy*; D008934:Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D000954:Antigens, Surface; D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2