TY - JOUR
T1 - Noninvasive imaging of human immune responses in a human xenograft model of graft-versus-host disease
AU - Van Elssen, Catharina H M J
AU - Rashidian, Mohammad
AU - Vrbanac, Vladimir
AU - Wucherpfennig, Kai W
AU - El Habre, Zeina
AU - Sticht, Jana
AU - Freund, Christian
AU - Jacobsen, Johanne
AU - Cragnolini, Juanjo
AU - Ingram, Jessica
AU - Plaisier, Loes
AU - Spierings, Eric
AU - Tager, Andrew M
AU - Ploegh, Hidde
N1 - © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2017/6
Y1 - 2017/6
N2 - The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer, or autoimmunity. Immuno-PET is a noninvasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets. Methods: We developed a method to noninvasively image human immune responses in a relevant humanized mouse model. We generated a camelid-derived single-domain antibody specific for human class II major histocompatibility complex products and used it to noninvasively image human immune cell reconstitution in nonobese diabetic severe combined immune deficiency g2/2 mice reconstituted with human fetal thymus, liver, and liver-derived hematopoietic stem cells (BLT mice). Results: We showed imaging of infiltrating immunocytes in BLT mice that spontaneously developed a graft-versus-host-like condition, characterized by alopecia and blepharitis. In diseased animals, we showed an increased PET signal in the liver, attributable to infiltration of activated class II major histocompatibility complex1 T cells. Conclusion: Noninvasive imaging of immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of graft-versus-host disease and holds promise for other diseases characterized by inflammation.
AB - The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer, or autoimmunity. Immuno-PET is a noninvasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets. Methods: We developed a method to noninvasively image human immune responses in a relevant humanized mouse model. We generated a camelid-derived single-domain antibody specific for human class II major histocompatibility complex products and used it to noninvasively image human immune cell reconstitution in nonobese diabetic severe combined immune deficiency g2/2 mice reconstituted with human fetal thymus, liver, and liver-derived hematopoietic stem cells (BLT mice). Results: We showed imaging of infiltrating immunocytes in BLT mice that spontaneously developed a graft-versus-host-like condition, characterized by alopecia and blepharitis. In diseased animals, we showed an increased PET signal in the liver, attributable to infiltration of activated class II major histocompatibility complex1 T cells. Conclusion: Noninvasive imaging of immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of graft-versus-host disease and holds promise for other diseases characterized by inflammation.
KW - Journal Article
KW - Single domain antibodies
KW - ImmunoPET
KW - GvHD
KW - Humanized mice
KW - Immunity, Innate/immunology
KW - T-Lymphocytes/immunology
KW - Humans
KW - Histocompatibility Antigens Class II/immunology
KW - Radiopharmaceuticals/immunology
KW - Mice, Knockout
KW - Graft vs Host Disease/diagnostic imaging
KW - Animals
KW - Single-Domain Antibodies/immunology
KW - Mice
KW - Positron-Emission Tomography/methods
KW - humanized mice
KW - single domain antibodies
UR - http://www.scopus.com/inward/record.url?scp=85020221878&partnerID=8YFLogxK
U2 - 10.2967/jnumed.116.186007
DO - 10.2967/jnumed.116.186007
M3 - Article
C2 - 28209904
SN - 0161-5505
VL - 58
SP - 1003
EP - 1008
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 6
ER -