Faculty Collaboration Database

Concurrent induction of CD4+ and CD8+ T cells during tumor growth with antitumor reactivity in adoptive immunotherapy. J Immunother 1997 Mar;20(2):138-45

Date

03/01/1997

Pubmed ID

9087386

DOI

10.1097/00002371-199703000-00006

Scopus ID

2-s2.0-0031463663 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

We have previously reported that the poorly immunogenic D5 melanoma transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) will elicit immunity in tumor-draining lymph node (TDLN) cells after subcutaneous inoculation. After in vitro activation with anti-CD3 and interleukin-2 (IL-2), these cells acquire in vivo antitumor reactivity to wild-type tumor in the adoptive immunotherapy of pulmonary metastases. Using monoclonal antibodies, depletion of CD4+ or CD8+ T cells immediately after the adoptive transfer of activated TDLN cells revealed that both subsets could mediate the regression of tumor in the absence of exogenous IL-2 administration. CD8+ cells were more potent than CD4+ cells in mediating tumor regression on a per cell basis. We found that the exogenous administration of IL-2 enhanced the antitumor efficacy of CD4+ T cells. Purified CD4+ and CD8+ TDLN cells that were activated separately in culture released GM-CSF and interferon-gamma in response to wild-type tumor in vitro and mediated tumor regression in vivo. Last, the induction of either immune CD4+ or CD8+ T-cell subset during growth of the GM-CSF-secreting melanoma was found to be unaffected by the depletion of the alternate T-cell subset before tumor inoculation. These findings demonstrate that both CD4+ and CD8+ T cells can independently acquire therapeutic reactivity and presumably recognize two separate epitopes involved in tumor rejection.

Author List

Arca MJ, Krauss JC, Aruga A, Cameron MJ, Chang AE

MESH terms used to index this publication - Major topics in bold

Animals
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Division
Female
Immunotherapy, Adoptive
Lymphocyte Count
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Tumor Cells, Cultured