Elimination of cycling CD4+ suppressor T cells with an anti-mitotic drug releases non-cycling CD8+ T cells to cause regression of an advanced lymphoma

Immunology. 1990 Sep;71(1):90-5.

Abstract

This paper describes a model of successful immunotherapy of advanced lymphoma based on the selective elimination of cycling tumour-induced suppressor T cells. It shows that a single injection of the anti-mitotic drug, vinblasting (Vb), results in complete regression of a large L5178Y lymphoma and its metastases, but not if it is growing in an immunocompetent host. Vb-induced, immunologically mediated tumour regression was dependent on the anti-tumour function of CD8+ T cells, because regression was prevented by depleting the host of this subset of T cells 24 hr after Vb was given. Regression was also prevented by infusing the host with Vb-sensitive, CD4+ T cells from a tumour-bearing donor. These and other results are in keeping with the interpretation that Vb-induced regression of the L5178Y lymphoma depends on the ability of the drug to eliminate CD4+ suppressor T cells that are replicating, and to spare non-replicating CD8+ effector cells. It is suggested that at an advanced stage of growth of the L5178Y lymphoma the host possesses an acquired population of antigen-primed CD8+ effector T cells that are unable to become activated in response to abundant tumour antigen because of the dominant influence of CD4+ suppressor cells. Activation of these CD8+ T cells was indicated by the finding that they were rapidly converted from being cyclophosphamide (Cy) resistant to being highly Cy sensitive within 48 hr of giving Vb.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • CD4 Antigens / analysis
  • CD8 Antigens
  • Drug Administration Schedule
  • Female
  • Immune Tolerance / drug effects*
  • Immunocompetence
  • Leukemia L5178 / immunology
  • Leukemia L5178 / pathology
  • Leukemia L5178 / therapy*
  • Mice
  • Mice, Inbred Strains
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / drug effects*
  • Vinblastine / administration & dosage
  • Vinblastine / therapeutic use*

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Vinblastine