Idiotype immunization combined with granulocyte-macrophage colony- stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses

Anders Österborg, Qing Yi, Lotta Henriksson, Jan Fagerberg, Susanne Bergenbrant, Mahmood Jeddi-Tehrani, Ulla Rudén, Ann Kari Lefvert, Göran Holm, Håkan Mellstedt

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

Idiotypic structures expressed on the myeloma Ig protein might be regarded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimulating factor(GM-CSF). All patients developed an idiotype (Id)-specific T-cell Immunity, defined as blood T cells predominantly secreting interferon-γ (IFN-γ) and interleukin-2 (IL-2) (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed-type hypersensitivity against the Id was not evoked. The specific IFN-γ/IL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibility complex (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37% inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T cells recognized peptides corresponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producing IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly MHC class I-restricted type I T-cell response.

Original languageEnglish (US)
Pages (from-to)2459-2466
Number of pages8
JournalBlood
Volume91
Issue number7
DOIs
StatePublished - Apr 1 1998

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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