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Introduction Primary biliary cholangitis (PBC) is characterized by lymphocyte cell-induced immune destruction of cholangiole. However, the immunological characteristics of peripheral blood cells in PBC patients remain unknown. This study was designed to reveal the differences in the immunological characteristics between PBC patients and healthy adults. Methods We performed high-throughput sequencing to determine the TRB–CDR3 and IGH–CDR3 repertoires of T and B cells in 19 healthy controls and 29 PBC patients. Different immunological characteristics, such as distinctive complementarity determining region 3 (TRB–CDR3) lengths, usage bias of V and J segments, and random nucleotide addition were identified in PBC and healthy control (HC) groups. Results The diversity of TRB–CDR3 was significantly lower in the PBC group compared with the HC group. CDR3 and the N addition length distribution were significantly changed compared with the HC group. It appeared that the PBC group had more short N additions and the HC group had more long N additions in the TRB–CDR3 repertoire. The results also revealed a set of PBC-associated clonotypes compared with the HC group. Conclusion This study suggested that PBC is a complex autoimmune disease process with evidence of different TRB–CDR3 rearrangements compared with healthy adults that share IGH–CDR3 peptides with some autoimmune diseases. This new insight may contribute to a better understanding of the immune functions of PBC patients and benefit efficient applications of PBC diagnosis and treatments.

Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.

Impaired immune reconstitution following allogeneic bone marrow transplantation (BMT) remains a major obstacle to its clinical application. In this study, interleukin (IL)-7-transduced bone marrow stromal cells (MSC-IL7, 1 x 10(6)/mouse) were transfused into lethally irradiated C57BL/6 recipient mice. By day 40 after transplantation, the recipient mice were challenged with the lymphoma cell line EL4. MSC-IL7 co-transplantation protected recipient mice from leukemic mortality (MST120 days after BMT vs mean survival time (MST) 70 days in the PBS group) It enhance the PFC count and DTH responses of recipients after transplantation. In conclusion, MSC mediated IL-7 gene therapy and may be a more feasible strategy to restore immune function following allo-TCD-BMT.