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Med. Sci. 2014, 2(2), 82-97; doi:10.3390/medsci2020082
Article

NKT Cell Responses to B Cell Lymphoma

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1 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 2 Department of Medicine and the Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
* Author to whom correspondence should be addressed.
Received: 4 October 2013 / Revised: 8 March 2014 / Accepted: 25 March 2014 / Published: 14 April 2014
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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Abstract

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.
Keywords: NKT cells; CD1d; mouse models of lymphoma; mantle cell lymphoma; α-galactosylceramide NKT cells; CD1d; mouse models of lymphoma; mantle cell lymphoma; α-galactosylceramide
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Li, J.; Sun, W.; Subrahmanyam, P.B.; Page, C.; Younger, K.M.; Tiper, I.V.; Frieman, M.; Kimball, A.S.; Webb, T.J. NKT Cell Responses to B Cell Lymphoma. Med. Sci. 2014, 2, 82-97.

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