Graft-versus-host disease pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The pathophysiology of GvHD is based upon immune activation and inflammation due | The pathophysiology of GvHD is based upon immune activation and inflammation due to donor-derived T cell responses, ultimately resulting in host organ damage.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
The pathophysiology involves donor alloreactive T lymphocytes mount an immune attack against recipient tissue.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> The most common tissues affected are the skin, liver, and gastrointestinal tract.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> Tissues of cardiac, skeletal muscle, or neurologic origin are typically not affected.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> Donor T cells can recognize an antigen presenting cell ([[APC]]) harboring a minor histocompatibility antigen ([[miHA]]). miHA are short protein fragments that are derived from intracellular proteins. When donor-derived T cells interact with these miHAs, the immune response is activated.<ref name="pmid12021249">{{cite journal| author=Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG| title=Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. | journal=J Clin Invest | year= 2002 | volume= 109 | issue= 10 | pages= 1335-44 | pmid=12021249 | doi=10.1172/JCI14989 | pmc=150980 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12021249 }} </ref> CD4+ T cells recognize miHAs on MHC class II molecules, and CD8+ T cells recognize miHAs on MHC class I molecules. Both CD4+ and CD8+ T cells are known to play an important role in GvHD pathogenesis. Though both host and recipient APCs are present in a patient after a transplant, the host APCs are the key cells that allow for antigen presentation | The pathophysiology involves donor alloreactive T lymphocytes mount an immune attack against recipient tissue.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> The most common tissues affected are the skin, liver, and gastrointestinal tract.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> Tissues of cardiac, skeletal muscle, or neurologic origin are typically not affected.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> Donor T cells can recognize an antigen presenting cell ([[APC]]) harboring a minor histocompatibility antigen ([[miHA]]). APCs are typically dendritic cells, which are professional APCs.<ref name="pmid18596226">{{cite journal| author=Yi T, Zhao D, Lin CL, Zhang C, Chen Y, Todorov I et al.| title=Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease. | journal=Blood | year= 2008 | volume= 112 | issue= 5 | pages= 2101-10 | pmid=18596226 | doi=10.1182/blood-2007-12-126987 | pmc=2518909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596226 }} </ref> miHA are short protein fragments that are derived from intracellular proteins. When donor-derived T cells interact with these miHAs, the immune response is activated.<ref name="pmid12021249">{{cite journal| author=Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG| title=Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. | journal=J Clin Invest | year= 2002 | volume= 109 | issue= 10 | pages= 1335-44 | pmid=12021249 | doi=10.1172/JCI14989 | pmc=150980 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12021249 }} </ref> CD4+ T cells recognize miHAs on MHC class II molecules, and CD8+ T cells recognize miHAs on MHC class I molecules. Both CD4+ and CD8+ T cells are known to play an important role in GvHD pathogenesis. Though both host and recipient APCs are present in a patient after a transplant, the host APCs are the key cells that allow for antigen presentation | ||
An important component in the immune response is the Th1-type subset and its cytokines TNF-alpha, IL-2, and interferon-gamma. A Th2-type profile can suppress GvHD.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> | An important component in the immune response is the Th1-type subset and its cytokines TNF-alpha, IL-2, and interferon-gamma. A Th2-type profile, which includes IL-4, IL-5, IL-6, IL-10, and IL-13, can suppress GvHD.<ref name="pmid23593203">{{cite journal| author=Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R et al.| title=The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease. | journal=PLoS One | year= 2013 | volume= 8 | issue= 4 | pages= e60367 | pmid=23593203 | doi=10.1371/journal.pone.0060367 | pmc=3617218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23593203 }} </ref> <ref name="pmid18596226">{{cite journal| author=Yi T, Zhao D, Lin CL, Zhang C, Chen Y, Todorov I et al.| title=Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease. | journal=Blood | year= 2008 | volume= 112 | issue= 5 | pages= 2101-10 | pmid=18596226 | doi=10.1182/blood-2007-12-126987 | pmc=2518909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596226 }} </ref> There are some exceptions to this observation, as elimination of interferon-gamma can enhance GvHD and loss of IL-4 can reduce GvHD. | ||
The programmed death-1 (PD-1) pathway is an immune checkpoint pathway that functions to suppress alloreactive T cells. | The programmed death-1 (PD-1) pathway is an immune checkpoint pathway that functions to suppress alloreactive T cells. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]
Overview
The pathophysiology of GvHD is based upon immune activation and inflammation due to donor-derived T cell responses, ultimately resulting in host organ damage.[1]
Pathophysiology
The pathophysiology involves donor alloreactive T lymphocytes mount an immune attack against recipient tissue.[1] The most common tissues affected are the skin, liver, and gastrointestinal tract.[1] Tissues of cardiac, skeletal muscle, or neurologic origin are typically not affected.[1] Donor T cells can recognize an antigen presenting cell (APC) harboring a minor histocompatibility antigen (miHA). APCs are typically dendritic cells, which are professional APCs.[2] miHA are short protein fragments that are derived from intracellular proteins. When donor-derived T cells interact with these miHAs, the immune response is activated.[3] CD4+ T cells recognize miHAs on MHC class II molecules, and CD8+ T cells recognize miHAs on MHC class I molecules. Both CD4+ and CD8+ T cells are known to play an important role in GvHD pathogenesis. Though both host and recipient APCs are present in a patient after a transplant, the host APCs are the key cells that allow for antigen presentation
An important component in the immune response is the Th1-type subset and its cytokines TNF-alpha, IL-2, and interferon-gamma. A Th2-type profile, which includes IL-4, IL-5, IL-6, IL-10, and IL-13, can suppress GvHD.[1] [2] There are some exceptions to this observation, as elimination of interferon-gamma can enhance GvHD and loss of IL-4 can reduce GvHD.
The programmed death-1 (PD-1) pathway is an immune checkpoint pathway that functions to suppress alloreactive T cells.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Al-Chaqmaqchi H, Sadeghi B, Abedi-Valugerdi M, Al-Hashmi S, Fares M, Kuiper R; et al. (2013). "The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease". PLoS One. 8 (4): e60367. doi:10.1371/journal.pone.0060367. PMC 3617218. PMID 23593203.
- ↑ 2.0 2.1 Yi T, Zhao D, Lin CL, Zhang C, Chen Y, Todorov I; et al. (2008). "Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease". Blood. 112 (5): 2101–10. doi:10.1182/blood-2007-12-126987. PMC 2518909. PMID 18596226.
- ↑ Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG (2002). "Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease". J Clin Invest. 109 (10): 1335–44. doi:10.1172/JCI14989. PMC 150980. PMID 12021249.