Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell-depleted haploidentical SCT. Eight patients were treated at 10(4) cells/kg/dose, and 8 patients received 10(5) cells/kg/dose. Patients receiving 10(5) cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 10(4) cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA(-)CCR-7(-)) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell-receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vbeta repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach.
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PMID:Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. 1674 Dec 53

One major limitation of UCBT is the lack of donor cells available for posttransplantation donor leukocyte infusions (DLI) to boost immunity or induce graft-versus-leukemia (GVL) activity. Starting from a approximately 5% fraction of a UCB graft, we report the feasibility and biological characteristics of ex vivo expansion of frozen/thawed CB T cells by anti-CD3 and anti-CD28 antibody-coated Dynal beads in the presence of interleukin (IL)-2. We postulated that while undergoing expansion, UCB T cells may mature toward a Th1/Tc1 phenotype and acquire the potential for cytotoxicity. Whereas an almost 2-log expansion also led to the acquisition of IL-12Ralpha and an increase in Th1 characteristics, postexpansion lymphocytes produced less interferon-gamma, tumor necrosis factor-alpha, and granzyme B; stored almost no perforin; and lacked cytotoxicity against allogeneic targets. Collectively, these suggest relative safety from acute/hyperacute graft-versus-host disease. CD8(+) T cells expanded preferentially, whereas a higher rate of apoptosis in CD4(+) T cells also promoted an inverted CD4/CD8 ratio. Most expanded T cells retained expression of CD27, CD28, and L-selectin but down-regulated CCR-7. In summary, UCB T cell proliferation sustained by CD3/CD28 co-stimulatory beads and IL-2 can lead to clinically relevant doses of DLI from a very small fraction of the UCB graft, although future strategies to reduce apoptosis may enhance their clinical potential.
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PMID:Ex vivo expansion and Th1/Tc1 maturation of umbilical cord blood T cells by CD3/CD28 costimulation. 1880 50