Compartmentalization of allogeneic T-cell responses in the bone marrow and spleen of humanized NOD/SCID mice containing activated human resident myeloid dendritic cells.

Vuckovic, S., Wahid, F.S.A., Rice, A. M., Kato, M., Khalil, D., Rodwell, R. and Hart, D. N. J. (2008) Compartmentalization of allogeneic T-cell responses in the bone marrow and spleen of humanized NOD/SCID mice containing activated human resident myeloid dendritic cells.. Experimental Hematology, 36 11: 1502-1512. doi:10.1016/j.exphem.2008.06.011


Author Vuckovic, S.
Wahid, F.S.A.
Rice, A. M.
Kato, M.
Khalil, D.
Rodwell, R.
Hart, D. N. J.
Title Compartmentalization of allogeneic T-cell responses in the bone marrow and spleen of humanized NOD/SCID mice containing activated human resident myeloid dendritic cells.
Journal name Experimental Hematology   Check publisher's open access policy
ISSN 0301-472X
1873-2399
Publication date 2008-11-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.exphem.2008.06.011
Open Access Status Not yet assessed
Volume 36
Issue 11
Start page 1502
End page 1512
Total pages 11
Place of publication New York, NY, U.S.A.
Publisher Elsevier Inc.
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
110706 Immunogenetics (incl. Genetic Immunology)
1102 Cardiovascular Medicine and Haematology
Formatted abstract
Objective.
Human allogeneic (allo)–T-cell responses within recipient lymphoid tissues and the degree to which they are altered in the presence of activated tissue-resident dendritic cells (DC) remain unknown. This study examined allo–T-cell recruitment and the early allo–Tcell responses that occur in the bone marrow (BM) and spleen (SP) of humanized (hu) nonobese diabetic (NOD)/severe combined immunodeficient (SCID) recipients containing activated human tissue-resident myeloid DC (MDC).

Materials and Methods.
Human naïve allo–T cells were transferred into polyinosinic:polycytidylic acid [poly(I:C)]–treated or untreated huNOD/SCID recipients containing human tissue-resident DC derived from transplanted CD34+ cells. Activation of human tissue-resident MDC mediated by poly(I:C) treatment, recruitment, proliferation, and effector differentiation of allo–T cells in the BM and SP of huNOD/SCID recipients were analyzed in vivo by flow cytometry.

Results.
Poly(I:C) treatment induced transient activation of human MDC within a maximum of 8 hours, as evidenced in the BM by an increased proportion of MDC-expressing CD86 while in the SP by MDC expressing CD86 and producing interleukin-12. Poly(I:C)-pretreated hu-NOD/SCID recipients showed changes in the recruitment of allo–T cells in the BM and SP and developed different allo–T cell responses within the BM and SP compartments. In the BM, allo–T cells underwent multiple divisions and increased numbers of interferon-γ+ and tumor necrosis factor–α+ effector cells, while the majority of splenic allo–T cells underwent a single division and had fewer effector allo–T cells.

Conclusions.
Our experimental transplantation model demonstrates that early allo–T-cell responses are regulated by compartmentalization in the BM and secondary lymphoid tissues; events potentially occurring after allotransplantation in human recipients.
© 2008 ISEH -Society for Hematology and Stem Cells. Published by Elsevier Inc.
Keyword NOD/SCID
Dendritic Cells
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 08 Apr 2009, 23:51:15 EST by Joanne PRESTON on behalf of School of Medicine