Long-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patients.
OBJECTIVE
To elucidate long-term effects of idiotype (Id) vaccination on Id-specific T cells of multiple myeloma (MM) patients and compare Id-specific T-cell responses of peripheral blood with those of bone marrow (BM).


METHODS
Id-specific T-cell responses of peripheral blood mononuclear cells (PBMC) were compared with those of BM mononuclear cells (BMMC) in 10 MM patients vaccinated with the Id protein at a median time of 41 months since the last immunization. The PBMC responses at late follow-up were also compared with those during active immunization. The responses were assessed by a proliferation assay, enzyme-linked immunospot (ELISPOT) (gamma-interferon), cytometric bead array (CBA) for secreted cytokines and quantitative real-time polymerase chain reaction (QRT-PCR) for cytokine gene expression.


RESULTS
At the late testing time, an Id-specific response was detected in PBMC of five patients (ELISPOT, CBA, QRT-PCR) and in BMMC of four patients (CBA, QRT-PCR). A response in both compartments was noted only in three patients. The cytokines gene profile was consistent with a predominance of Th(2) cells [interleukin (IL)-4, IL-5, IL-10]. Comparison of the Id-specific responses of PBMC during active immunization with those at the late follow-up showed that the frequency and magnitude of the responses had decreased significantly by time (proliferation/ELISPOT) (P < 0.02) and shifted at the gene level from a Th(1) to a Th(2) profile (P < 0.05).


CONCLUSIONS
Id-specific T-cells may decline overtime and shift toward a Th(2) response and may be found at a similar frequency of patients in blood and BM.
Abdalla
Amir Osman
AO
Immune and Gene Therapy Laboratory, CCK, Karolinska University Hospital Solna, Stockholm, Sweden.
Hansson
Lotta
L
Eriksson
Ingrid
I
Näsman-Glaser
Barbro
B
Mellstedt
Håkan
H
Osterborg
Anders
A
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D019496:Cancer Vaccines; D016207:Cytokines; C052643:F(ab')2 receptor; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D011971:Receptors, Immunologic