Decreased Expression and Function of Vß6+ and Vß14+ T Cells is Associated with Decreased Th1 Cytokine Production in Mice with Plasma Cell Tumors

Abstract

Aims and background

We have found that polyclonally stimulated T cells from mice bearing ascitic plasma cell tumors demonstrate specific decreases in Th1 cytokine production. In this study we investigated whether loss of Th1 responses in the plasma cell tumor system was associated with alterations in the Vß T cell receptor repertoire.

Methods

We examined the cell surface expression of specific Vß expressing splenic CD4+ or CD8+ T cells from normal and tumor bearing mice using direct three-color flowcytometry. In order to determine the Th phenotype of Vß expressing T cells, we enriched for Vß6, Vß14 or Vß8.1,8.2 cells, polyclonally stimulated them and measured the levels of the cytokines interleukin-4 (IL-4), IL-2 and interferon-gamma (IFN-gamma).

Results

We find that there is a statistically significant decrease in the frequency of Vß6+ and Vß14+ CD8+ T cells in mice bearing a plasma cell tumor (B53) as compared to normals (p<0.05). Stimulated Vß6+ and Vß14+ T cells exhibit an exclusively Th1 phenotype. Stimulated Vß6+ and Vß14+ T cells from B53 mice are deficient in production of the Th1 cytokines. In contrast, stimulated Vß8.1,8.2+ T cells, which are not altered in B53 mice, reveal a Th2 phenotype.

Conclusions

The significance of this study is our demonstration that decreased expression and function of Vß6+ and Vß14+ T cells may be, at least in part, responsible for the decrease in the production of IL-2 and/or IFN-gamma observed in hosts with tumors.