Alloresponse, an immune response with unique strength and diversity to non-self antigens from members of the same species, is caused by the extensive difference of polymorphic genes between the allogeneic donor and recipient, primarily the major histocompatibility complex (MHC). As the central mediators of alloresponses, alloreactive T cells acquire self MHC restriction and the capability to recognize non-self MHC, leading to graft rejection and graft-versus-host-disease (GVHD), two major barriers to the continued success of solid organ and hematopoietic stem cell transplantation (HSCT). Another key player in perpetuating alloimmune responses are B cells. Differentiation and maturation of recipient B cells into plasma cells promote the production of donor-specific antibodies (DSA), which are the leading cause of acute and chronic transplant tissue injury. B cells also have substantiated roles in chronic GVHD pathogenesis following allogeneic HSCT through the production of autoantibodies that trigger organ fibrosis, interaction with T cells to present alloantigens, and modulation of the T cell response by secreting cytokines.
Both T and B cells express an enormous diversity of antigen-specific receptors: T-cell receptor (TCR) for T cells and B-cell receptor (BCR) for B cells, which are created through somatic gene rearrangement and form the basis of the host’s ability to cope with innumerable immunologic threats. Earlier studies tracking alloresponses in humans were limited by the technical challenges of low resolution and unsatisfaction to replicate the in vivo setting to produce consistent correlations with clinical outcomes. Only recently have the advances in next-generation sequencing (NGS) technologies, with high robustness and reproducibility, opened up new possibilities to provide a precise picture of the tremendously diverse immune repertoire and to tackle fundamental questions of T cell and B cell alloimmunity in animals and humans. Emerging sequencing techniques and platforms at the single-cell and bulk population levels also allow the investigation of unconventional gamma delta T cells, the role of which, in transplantation outcomes is largely under-researched.
This Research Topic aims to collect Original Research and state-of-the-art Review and Mini-Review articles on the recent advances of immunogenomics after solid organ and HSCT, including, but not limited to, the following sub-topics:
1. Immune and receptor repertoire profiling of alpha beta T cells and their roles in mediating alloresponses after transplantation in preclinical and clinical settings.
2. Immune and receptor repertoire profiling of gamma delta T cells and their roles in graft rejection, GVHD and host immune defense after transplantation.
3. Immune and receptor repertoire profiling of B cells and plasma cells to evaluate their roles in antibody-mediated rejection and GVHD induction after transplantation.
4. Multiomic single cell and spatial characterization of T cell and B cell after solid organ and HSCT.
5. Effect of immunosuppression and pre-conditioning regimens on the reconstitution of T cell and B cell immune repertoires after transplantation and its association with outcomes.
6. Utilization of immune repertoire profiling of T cell and B cell to guide clinical diagnosis and personalized medicine after transplantation.
7. Advances and limitations of novel sequencing platforms to evaluate immune receptor repertoire to understand the immunological basis for transplantation disease conditions.
Alloresponse, an immune response with unique strength and diversity to non-self antigens from members of the same species, is caused by the extensive difference of polymorphic genes between the allogeneic donor and recipient, primarily the major histocompatibility complex (MHC). As the central mediators of alloresponses, alloreactive T cells acquire self MHC restriction and the capability to recognize non-self MHC, leading to graft rejection and graft-versus-host-disease (GVHD), two major barriers to the continued success of solid organ and hematopoietic stem cell transplantation (HSCT). Another key player in perpetuating alloimmune responses are B cells. Differentiation and maturation of recipient B cells into plasma cells promote the production of donor-specific antibodies (DSA), which are the leading cause of acute and chronic transplant tissue injury. B cells also have substantiated roles in chronic GVHD pathogenesis following allogeneic HSCT through the production of autoantibodies that trigger organ fibrosis, interaction with T cells to present alloantigens, and modulation of the T cell response by secreting cytokines.
Both T and B cells express an enormous diversity of antigen-specific receptors: T-cell receptor (TCR) for T cells and B-cell receptor (BCR) for B cells, which are created through somatic gene rearrangement and form the basis of the host’s ability to cope with innumerable immunologic threats. Earlier studies tracking alloresponses in humans were limited by the technical challenges of low resolution and unsatisfaction to replicate the in vivo setting to produce consistent correlations with clinical outcomes. Only recently have the advances in next-generation sequencing (NGS) technologies, with high robustness and reproducibility, opened up new possibilities to provide a precise picture of the tremendously diverse immune repertoire and to tackle fundamental questions of T cell and B cell alloimmunity in animals and humans. Emerging sequencing techniques and platforms at the single-cell and bulk population levels also allow the investigation of unconventional gamma delta T cells, the role of which, in transplantation outcomes is largely under-researched.
This Research Topic aims to collect Original Research and state-of-the-art Review and Mini-Review articles on the recent advances of immunogenomics after solid organ and HSCT, including, but not limited to, the following sub-topics:
1. Immune and receptor repertoire profiling of alpha beta T cells and their roles in mediating alloresponses after transplantation in preclinical and clinical settings.
2. Immune and receptor repertoire profiling of gamma delta T cells and their roles in graft rejection, GVHD and host immune defense after transplantation.
3. Immune and receptor repertoire profiling of B cells and plasma cells to evaluate their roles in antibody-mediated rejection and GVHD induction after transplantation.
4. Multiomic single cell and spatial characterization of T cell and B cell after solid organ and HSCT.
5. Effect of immunosuppression and pre-conditioning regimens on the reconstitution of T cell and B cell immune repertoires after transplantation and its association with outcomes.
6. Utilization of immune repertoire profiling of T cell and B cell to guide clinical diagnosis and personalized medicine after transplantation.
7. Advances and limitations of novel sequencing platforms to evaluate immune receptor repertoire to understand the immunological basis for transplantation disease conditions.