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

ObjectiveHuman 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 MethodsHuman 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.ResultsPoly(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.ConclusionsOur 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.