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).Materials and Methods. Human naive 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 interieukin-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. (c) 2008 ISEH Society for Hematology and Stem Cells. Published by Elsevier Inc.