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Adoptive immunotherapy with interleukin-2 (IL-2) results in diminished IL-2 production by stimulated peripheral blood
R Kradin1, J Kurnick, J Gifford
1Department of Medicine, Massachusetts General Hospital, Boston 02114.
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.
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.