Immune evasion from NK surveillance related to inadequate NK-cell function has 
been suggested as an explanation of the high incidence of relapse and fatal 
outcome of many blood malignancies. In this report we have used Jurkat and Raji 
cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B 
cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow 
cytometry we show that Jurkat and Raji cells constitutively express mRNA and 
protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and 
up-regulate the expression in a cell-line specific and stress-specific manner. 
Furthermore, we revealed by electron microscopy, immunoflow cytometry and 
western blot that these ligands were expressed and secreted on exosomes, 
nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D 
ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated 
cytotoxicity and thus impair NK-cell function. Interestingly, thermal and 
oxidative stress enhanced the exosome secretion generating more soluble NKG2D 
ligands that aggravated the impairment of the cytotoxic response. Taken 
together, our results might partly explain the clinically observed NK-cell 
dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of 
thermal and oxidative stress, enhancing the release of immunosuppressive 
exosomes, should be considered when cytostatic and hyperthermal anti-cancer 
therapies are designed.