Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alemtuzumab (anti-CD52; Campath 1-H) depletes both host and donor T cells when used in preparative regimens for allogeneic transplantation. This promotes engraftment even after nonmyeloablative conditioning and limits graft-versus-host disease (GVHD) even after unrelated or major histocompatibility complex (MHC) disparate allografts. We asked whether anti-CD52 differentially targets antigen-presenting cells (APCs), in addition to depleting T cells. Monocyte-derived dendritic cells (moDCs) expressed abundant CD52 as expected. Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs), however, never expressed CD52. Immunostaining of skin and gut confirmed the absence of CD52 on these resident DC populations under both steady-state and inflammatory conditions. Although anti-CD52 functions primarily by antibody-dependent cellular cytotoxicity (ADCC) in vivo, assessment of its activity in vitro included complement-dependent lysis of CD52(+) cells. Anti-CD52 did not impair DC-T-cell adhesion, diminish DC-stimulated T-cell proliferation, or alter moDC development in vitro. We propose that anti-CD52 abrogates GVHD not only by T-cell depletion, but also by removing moDCs and their precursors. This would mitigate moDC phagocytosis and presentation of host-derived antigens to donor T cells in the inflammatory peritransplantation environment, thereby limiting GVHD. The sparing of LCs and DDC-IDCs by anti-CD52, as well as the recovery of donor-derived moDCs in a less inflammatory environment later after transplantation, may allow all these DCs to exert formative roles in graft-versus-tumor (GVT) reactions and immune reconstitution. Whether these results support a separation of deleterious from beneficial graft-host interactions at the level of antigen presentation, rather than solely at the level of T cells, will require further evaluation.
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PMID:Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. 1239 88

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.
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PMID:Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. 2254 51