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, Slavica; Abdul Wahid, Fadilah S.; Rice, Alison; Kato, Masato; Khalil, Dalia; Rodwell, Robyn; Hart, Derek N.J.

doi:10.1016/j.exphem.2008.06.011

« Previous Next »Experimental Hematology
Volume 36, Issue 11 , Pages 1496-1506, November 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

Slavica Vuckovic
- Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia
- Offprint requests to: Slavica Vuckovic, Ph.D., Mater Medical Research Institute, Dendritic Cell Program, Aubigny Place, Raymond Tce, South Brisbane, QLD 4101, Australia
Fadilah S. Abdul Wahid
- Cell Therapy Center, Hospital University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
Alison Rice
- Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia
Masato Kato
- Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia
Dalia Khalil
- Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia
Robyn Rodwell
- Queensland Cord Blood Bank, Mater Health Services, South Brisbane, Queensland, Australia
Derek N.J. Hart
- Mater Medical Research Institute, Dendritic Cell Program, South Brisbane, Queensland, Australia

Received 14 January 2008; received in revised form 27 May 2008; accepted 18 June 2008. published online 21 August 2008.

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).

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 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-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.