Age matters: Young T lymphocytes offer better protection from myeloma proliferation.

Alexander F Glick,John Lillvis,Pat Zanzonico,Yan S Song,Roger N Pearse,Paul Szabo,Camil Fuchs,Brian Hwang,Marc E Weksler

doi:10.1186/1742-4933-10-5

Abstract

BackgroundThe incidence and growth of cancer has been reported to increase with age and/or impaired T lymphocyte function.ResultsConsistent with these observations, we found that a monoclonal serum immunoglobulin (mIgG2b), rarely detectable after the injection of 5T33 murine multiple myeloma (MMM) cells into 3–4 month old wild-type C57BL/6 mice was seen more frequently in 18–20 month old wild-type C57BL/6 mice and in 3–4 month old Rag1-deficient C57BL/6 mice. These observations were confirmed and extended using more sensitive assays such as quantitation of splenic mRNA specific for the canonical 5T33 monoclonal IgG2b produced by 5T33 myeloma cells and the most sensitive assay, photon-imaging of mice injected with 5T33 cells, stably transfected with fire-fly luciferase gene (5T33L cells), which emit photons after the injection of luciferin. Furthermore, the proliferation of 5T33L myeloma cells in Rag1-deficient C57BL/6 mice was greater in mice which also received spleen T cells from 18–20 month old C57BL/6 wild-type mice compared to mice which received splenic T cells from 3–4 month old C57BL/6 wild-type mice. Thus, immune reconstitution of C57BL/6 mice with splenic T cells from young wild-type mice offered greater protection from progressive growth of 5T33L myeloma cells than did reconstitution with splenic T cells from old mice.ConclusionsOur findings support the hypothesis that age-associated changes in splenic T cell function contribute to the increased growth of 5T33 MMM cells in old compared to young C57BL/6 mice. Should similar processes occur in humans, increasing the anti-myeloma activity of T cells in old patients with multiple myeloma or transferring cryopreserved, young, autologous, T cells might benefit elderly patients with multiple myeloma.

Highlights

The incidence and growth of cancer has been reported to increase with age and/or impaired T lymphocyte function
We report that the ageassociated increase in the growth of 5T33 multiple myeloma (MMM) cells in old C57BL/6 mice reflects impaired immune surveillance associated with senescence of T lymphocytes
Growth of 5T33 MMM cells in C57BL/6 mice is influenced by age and T lymphocyte immune senescence The growth of 5T33 MMM cells in C57BL/6 female mice is reflected in the level of the specific monoclonal IgG2B produced by the 5T33 MMM cells that can be detected by serum protein electrophoresis (SPEP)

Summary

Introduction

The incidence and growth of cancer has been reported to increase with age and/or impaired T lymphocyte function. The frequency of human cancer, in general, and in multiple myeloma, in particular, increases exponentially with age through the eighth decade of life [1,2]. A similar phenomenon has been observed in experimental animals. Pristane induces more plasmacytomas in old than in young mice [3]. The exponential increase in cancer with age implies that two or more ageassociated factors contribute to the increased rate of development of neoplasms late in life. One age-associated factor in carcinogenesis is the accrual of genetic aberrations associated with the sequential transition of normal tissues to benign neoplasms and to malignant neoplasms [4]. The link between a sequential appearance of genetic

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