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


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 huNOD/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-gamma(+) and tumor necrosis factor-alpha(+) 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.
Vuckovic
Slavica
S
Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia. slavica.vuckovic@mmri.mater.org.au
Abdul Wahid
Fadilah S
FS
Rice
Alison
A
Kato
Masato
M
Khalil
Dalia
D
Rodwell
Robyn
R
Hart
Derek N J
DN
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D011070:Poly I-C