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.
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-gamma (IFN-gamma) 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-gamma/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.
Osterborg
A
A
Department of Oncology, Karolinska Hospital, Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Yi
Q
Q
Henriksson
L
L
Fagerberg
J
J
Bergenbrant
S
S
Jeddi-Tehrani
M
M
Rudén
U
U
Lefvert
A K
AK
Holm
G
G
Mellstedt
H
H
D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D015395:Histocompatibility Antigens Class I; D016178:Granulocyte-Macrophage Colony-Stimulating Factor