Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo.
We have developed a dual bioluminescent reporter system allowing noninvasive, concomitant imaging of T-cell trafficking, expansion, and activation of nuclear factor of activated T cells (NFAT) in vivo. NFAT activation plays an important role in T-cell activation and T-cell development. Therefore we used this system to determine spatial-temporal activation patterns of (1) proliferating T lymphocytes during graft-versus-host disease (GVHD) and (2) T-cell precursors during T-cell development after allogeneic hematopoietic stem cell transplantation (HSCT). In the first days after HSCT, donor T cells migrated to the peripheral lymph nodes and the intestines, whereas the NFAT activation was dominant in the intestines, suggesting an important role for the intestines in the early stages of alloactivation during development of GVHD. After adoptive transfer of in vitro-derived T-cell receptor (TCR) H-Y transgenic T-cell precursors into B6 (H-2(b)) hosts of both sexes, NFAT signaling and development into CD4(+) or CD8(+) single-positive cells could only be detected in the thymus of female recipients indicating either absence of positive selection or prompt depletion of double-positive thymocytes in the male recipients. Because NFAT plays an important role in a wide range of cell types, our system could provide new insights into a variety of biologic processes.
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY;
Il-Kang
IK
Na
John C
JC
Markley
Jennifer J
JJ
Tsai
Nury L
NL
Yim
Bradley J
BJ
Beattie
Alexander D
AD
Klose
Amanda M
AM
Holland
Arnab
A
Ghosh
Uttam K
UK
Rao
Matthias T
MT
Stephan
Inna
I
Serganova
Elmer B
EB
Santos
Renier J
RJ
Brentjens
Ronald G
RG
Blasberg
Michel
M
Sadelain
Marcel R M
MR
van den Brink
D016475:3T3 Cells; D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D019169:Jurkat Cells; D016086:Lentivirus / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049449:Luminescence; D008163:Luminescent Measurements / Q000379:methods; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D011401:Promoter Regions, Genetic / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D050778:NFATC Transcription Factors; D008156:Luciferases