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PMID: 9858522 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The central role of CD4(+) T cells in the antitumor immune response.

The Journal of experimental medicine ·Vol. 188 ·No. 12 ·1998-12-21 ·Pages 2357-68

Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H

Abstract

The induction of optimal systemic antitumor immunity involves the priming of both CD4(+) and CD8(+) T cells specific for tumor-associated antigens. The role of CD4(+) T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8(+) cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4(+) T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4(+) T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.

MeSH Terms
Animals Antigens, CD/genetics,immunology CD8-Positive T-Lymphocytes/immunology Cancer Vaccines/administration & dosage,immunology Cell Movement Cytokines/genetics,immunology Cytotoxicity, Immunologic Eosinophils/cytology,immunology Female Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage,immunology Injections, Subcutaneous Lymphocyte Cooperation Macrophages/cytology,enzymology,immunology,metabolism Melanoma, Experimental/immunology,pathology Mice Mice, Inbred C57BL Mice, Knockout NADPH Oxidases/genetics,metabolism Nitric Oxide Synthase/genetics,metabolism Nitric Oxide Synthase Type II T-Lymphocytes, Helper-Inducer/immunology
Chemicals
Antigens, CD Cancer Vaccines Cytokines Granulocyte-Macrophage Colony-Stimulating Factor Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse NADPH Oxidases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hung K
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hayashi R
Lafond-Walker A
Lowenstein C
Pardoll D
Levitsky H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.12.2357
Published
1998-12-21
Pages
2357-68
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212434
Subset
IM
Grants
NIAID NIH HHS · AI/AG37934-01 · United States
External Links
PubMed source DOI: 10.1084/jem.188.12.2357 PMC Full Text View journal details
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