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Query: UMLS:C0018133 (
graft-versus-host disease
)
18,032
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
T cell activation and cellular immune responses are modulated by interleukin 2 (IL2) through binding to its corresponding cell surface receptor. Three forms of the receptor are recognised based on IL2 binding affinity. The high affinity receptor is a heterotrimer composed of alpha, beta, and gamma(c)-polypeptide chains. The 55 kDa alpha-chain also known as the Tac (T cell activation) antigen or CD-25 is a unique subunit of the high affinity IL2 receptor (IL2Ralpha). Resting T cells express few IL2Ralpha, however, when activated, the expression of ILR2alpha rapidly increases. The IL2Ralpha is shed from the cell surface and is measurable in the serum as a 45 kDa soluble form (s-Tac or s-IL2Ralpha). Serum concentrations of s-Tac can be used as a surrogate marker for T cell activation and IL2Ralpha expression. IL2Ralpha is over expressed by T cells in a number of autoimmune diseases, allograft rejection and a variety of lymphoid neoplasms. IL2 induced proliferation of T cells can be inhibited by the murine monoclonal antibody (anti-Tac) directed against the alpha-chain of the
IL2R
. Through molecular engineering, murine anti-Tac has been humanised reducing its immunogenicity without changing its specificity. Humanised anti-Tac (HAT) has been shown to reduce the incidence of renal and cardiac allograft rejection as well as decrease the severity of
graft versus host disease
in patients undergoing HLA matched allogeneic bone marrow transplantation. IL2Ralpha targeted treatment with radioimmunoconjugates of anti-Tac and immunotoxins has shown promise in the treatment of CD25 expressing lymphomas.
...
PMID:Advances in interleukin 2 receptor targeted treatment. 1105
To study the canine immune system we generated a mouse model engrafted with canine lymphocytes using NOD SCID
IL2R
common gamma chain -/- (NSG) mice as recipients (Ca-PBL-SCID). Engraftment of canine peripheral blood lymphocytes (PBLs) was determined post-injection with 10(7) peripheral blood mononuclear cells (PBMCs) into irradiated NSG mice using flow cytometry and fluorescently labeled antibodies specific to canine helper T cells (CD45(+) CD4(+)), cytotoxic lymphocytes (CD45(+) CD8(+)), regulatory T cells (CD45(+) CD4(+) Foxp3(+)), and B cells (CD45(+) Ig(+) CD21lo). Canine CD45(+) lymphocytes were detectable as early as day 1 in the peritoneal cavity, and beginning at 9 days in the blood, bone marrow, and spleen. CD4(+) T cells, of which Foxp-3(+) CD25hi cells constituted a minor percentage, were the predominant lymphocyte population at 9 days post engraftment contrasting with increasing proportions of CD8(+) CTL's and Ig(+) B cells beginning at 16 days. Canine immunoglobulin was initially detected in the serum of Ca-PBL-SCID mice at 9 days post-engraftment and peaked in concentration at day 36. From day 28 to 52 post-engraftment 30% of the Ca-PBL-SCID mice became markedly anemic and thrombocytopenic, yet gross and histopathologic examination of bone marrow, kidneys, spleen, liver, and intestine revealed no obvious lesions. Blood smear evaluation revealed agglutination of mature red blood cells, reticulocytes and a regenerative anemia. These findings demonstrate that NSG mice are capable of engraftment of canine PBLs yet develop
graft versus host disease
similar to Hu-PBL-SCID mice.
...
PMID:Engraftment of canine peripheral blood lymphocytes into nonobese diabetic-severe combined immune deficient IL-2R common gamma chain null mice. 2436 85
Anti-thymocyte globulin (ATG) is an established approach to decrease chronic
GVHD
(cGVHD), yet the exact mechanism is uncertain. To better understand the mechanism of action of ATG in preventing cGVHD, we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group (CBMTG) 0801 trial, which demonstrated a significant impact of ATG on cGVHD. In a separate companion biology study, we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients. Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21
low
B cells, CD56
bright
NK
reg
cells, and T
reg
cells ST2, osteopontin, soluble B-cell activating factor (sBAFF),
Interleukin-2 receptor
alpha (sCD25), T-cell immunoglobulin and mucin domain-3 (TIM-3), matrix metallopeptidase 3, ICAM-1, C-X-C motif chemokine 10 (CXCL10), and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56
bright
NK
reg
cells (P < .0001). T
reg
cells, conventional Th cells, CD21
low
B cells, and all plasma markers were not affected. In the populations most affected by ATG, changes in naive Th cells were associated with the later development of cGVHD. This analysis suggests that ATG primarily impacts on cGVHD through suppression of naive Th cell expansion after transplantation. These associations need to be validated in additional studies.
...
PMID:Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study. 3175 35
