Long-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patients

Eur J Haematol. 2007 Nov;79(5):371-81. doi: 10.1111/j.1600-0609.2007.00962.x. Epub 2007 Oct 3.

Abstract

Objectives: 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).

Materials and 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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Marrow / immunology*
  • Cancer Vaccines / therapeutic use*
  • Cell Proliferation
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoglobulin Fab Fragments / metabolism
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin Idiotypes / administration & dosage*
  • Leukocytes, Mononuclear / immunology*
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • Phenotype
  • Polymerase Chain Reaction
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Cancer Vaccines
  • Cytokines
  • F(ab')2 receptor
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Immunoglobulin Idiotypes
  • Receptors, Immunologic