Anti-lymphoma effect of gammadelta T cells.
During the last few years, our knowledge about the activation and control of non-major histocompatibility complex (MHC)-restricted innate effector lymphocytes (such as natural killer (NK) cells, NK T cells and gammadelta T cells) has advanced enormously and immunotherapeutic strategies based on these cell types receive more and more attention. Apart from NK cells, several lines of evidence indicate that T cells, which express an alternative T cell receptor (TCR) composed of a CD3-associated gammadelta heterodimer, also contribute to the innate immune defense against tumors. Human gammadelta T cells represent a small subset of T cells (1-10% of peripheral blood T cells) and differ from conventional MHC-restricted ass T cells in recognition of a unique set of antigens ("phosphoantigens") and the lack of requirement of classical antigen-presenting molecules. Besides their role in the innate immune response against pathogens based on the recognition of distinctive microbial metabolic products (metabolites of the non-mevalonate pathway of isoprenoid synthesis), Vgamma9Vdelta2 T cells that constitute the dominant fraction of gammadelta T cells in humans exert potent cytotoxic activity, especially against lymphoid malignancies, mediated by as yet only partially determined pathway(s) of tumor recognition. This article will review available evidence from pre-clinical and early clinical studies regarding the contribution of gammadelta T cells in the defense against lymphoid malignancies and highlights some important issues that need to be addressed in the future.
Kunzmann
Volker
V
Medizinische Poliklinik Wuerzburg, University of Wuerzburg, Klinikstrasse 6-8, 97070 Wuerzburg, Germany. kunzmann_v@medizin.uni-wuerzburg.de
Wilhelm
Martin
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007157:Immunologic Surveillance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008223:Lymphoma / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D016692:Receptors, Antigen, T-Cell, gamma-delta