NK Cell Effector Functions Regulation by Modulating nTreg Cell Population During Progressive Growth of Dalton’s Lymphoma in Mice

ABSTRACT

Natural killer (NK) cells are large granular lymphocytes of the innate immune system and play a pivotal role against virus-infected cells, microbial pathogens, and tumor cells. NK cells secrete several cytokine,s but IFN-γ secreted by NK cells play a vital role in the activation of the innate and adaptive immune systems. But during any infection or tumor burden, functional activity of NK cells is downregulated significantly by nTreg cells. It is also found that during tumor progression, the number of nTreg cells increases as a result; it effectively suppresses the antitumor activity of NK cells. Therefore, in the present investigation, we intend to examine the mechanism of downregulation of antitumor immune response mediated by NK cells. We observed increased NK cell population at an early stage of Dalton’s lymphoma (DL) growth, while at late stage, NK cell numbers were decreased. The NK cell functional activity was govern by high level of IFN-γ measurement during tumor progression. The FoxP3⁺ CD25⁺ CD4⁺ T regulatory cell population was found to be continuously increased with high-level expression of FoxP3 during DL growth. The rapid increase in the number of Treg cells during DL progression may be due to high level of the FoxP3 transcription factor. The tumor microenvironment of DL cell progression has highly deleterious effect on NK cells after massive growth of tumor burden in BALB/c mice. This result also indicates that NK cell proliferation, activation, and accumulation are under the control of regulatory T cells.

KEYWORDS:

• Dalton’s lymphoma (DL) cells
• FoxP3
• IFN-γ
• Natural killer cells
• nTreg cells
• TGF-β

Acknowledgments

The authors thank Professor M.K. Thakur, Coordinator of ISLS, BHU (Department of Zoology, Banaras Hindu University, and Varanasi), for providing the instrumental facilities. We also acknowledge the use of real-time PCR facility and FACS machine of DBT-BHU Interdisciplinary School of Life Sciences, Banaras Hindu University. MST is a recipient of Senior Research Fellowship from the Center of advance study (CAS) under University Grant Commission (UGC), India. The work was supported by the grants from the Banaras Hindu University and University Grant Commission (UGC, P-01/669), Government of India to Professor A. Acharya.