Natural killer cells: amplifier or suppressor of graft-versus-host-disease symptoms?

Arsalan Jalili,1 Abbas hajifathali,2 Marzieh ebrahimi,3,*

1. Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
2. Hematopoeitic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3. Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Abstract

Introduction

Graft-versus-host disease (gvhd) is a routine complication after bone marrow transplantation and administration of other blood products. during gvhd cytotoxic t cells attack the hosts body cells. there different factors that should be considered to reduce the risk of graft-versus-host-disease like age, hla matching, hygiene, gender et al. according to the recent evidences, immune cells can be considered as a powerful therapeutic approach against different diseases and complications. natural killer cells (nk cells) are a kind of cytotoxic lymphocyte which are critical for innate immune system. nk cells provide rapid responses against viral-infected cells, infection and tumor cells. there are two main types of receptors on the surface of nk cells named inhibitory and activation receptors. and also there are some other types such as: co-inhibitory, co-activation receptors and immune checkpoint molecules. activation of each of these receptors can change the function of nk cells. activation of activation receptors by cancer cell, antigen presenting cells or any other stimulatory cells can make nk cells to release perforin, ldh, ifnγ and other factors which can cause the apoptosis and the death of stimulatory cell. on the other hand, targeting the inhibitory cells cause the exhaustion and inhibition of nk cells. as donors tcd8+ cells play a critical role in the complications of gvhd, this question was created that how nk cells are influenced in this condition and if these cells are helpful in suppression of gvhd side effects or escalation of them.

Methods

Relevant english-language literature were searched and retrieved from pubmed search engine (2010-2018). the following keywords were used: "graft-versus-host-disease", “gvhd”,”natural killer cells” and “nk cells”.

Results

Based on previous studies, the effect of nk cells on gvhd is controversial and is not clearly clarified, and that is because of its different reaction via apcs. if the inhibitory receptor nkg2a on the surface of nk cells bind to hla-e on the surface of apcs, it can cause the release of ifnγ and tnf-α. they make t cells to release perforin which cause tissue damage. on the other hand, if the activation receptor nkg2c on nk cells be bind to hla-e on the surface of gvhd , can cause the binding between nk cells and t cells and the release of perforin by nk cells which leads to the protection of tissues against gvhd.

Conclusion

Despite major efforts undertaken during this project for better understanding of nk cells function during gvhd, the role of nk cells during remained elusive because of conflicting evidence coming from different experimental approaches. nk cells are capable of both effector and regulatory functions. this dual nature of nk cells is likely responsible for the variable and even conflicting roles nk cells during gvhd.

Keywords

Graft-versus-host-disease, natural killer cells, bone marrow transplantation.