Publications by authors named "Charlotte F Inman"
Allogeneic immune responses underlie the graft-versus-leukaemia effect of stem cell transplantation, but disease relapse occurs in many patients. Minor histocompatibility antigen (mHAg) peptides mediate alloreactive T cell responses and induce graft-versus-leukaemia responses when expressed on patient haematopoietic tissue. We vaccinated nine HA-1-negative donors against HA-1 with a 'prime-boost' protocol of either two or three DNA 'priming' vaccinations prior to 'boost' with modified vaccinia Ankara (MVA).
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- Alemtuzumab is a targeted therapy that depletes certain T cells, leading to the emergence of CD52-negative (CD52-) T cells in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- The study analyzed blood samples from 67 patients, most with myeloid diseases, to explore the characteristics of CD52- T cells and their impact on clinical outcomes, finding that a notable percentage experienced acute and chronic graft-versus-host disease (GVHD).
- CD52- T cells predominantly consist of CD4 positive memory cells and display unique immune responses, with significant populations of these cells indicating a higher risk for developing acute GVHD in patients shortly after transplantation.
Background: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.
Methods: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma.
Transplantation is an effective treatment of many clinical disorders, but the mechanisms that regulate immunological tolerance are uncertain and remain central to improving patient outcome. Hemopoietic stem cell transplantation (SCT) often establishes "mixed chimerism" in which immune cells from both the donor and patient coexist in vivo in a setting of immunological tolerance. We studied immune function in 69 patients within 2 months following SCT; 37 were fully donor and 32 displayed mixed chimerism.
View Article and Find Full Text PDFAllogeneic stem cell transplantation (allo-SCT) can cure some patients with hematopoietic malignancy, but this relies on the development of a donor T cell alloreactive immune response. T cell activity in the first 2 weeks after allo-SCT is crucial in determining outcome, despite the clinical effects of the early alloreactive immune response often not appearing until later. However, the effect of the allogeneic environment on T cells is difficult to study at this time point due to the effects of profound lymphopenia.
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- Progesterone plays a crucial role in maintaining pregnancy by influencing maternal immune responses, particularly in tolerating the fetus, which is genetically different from the mother.
- Exposure of maternal T cells to physiological doses of progesterone alters their cytokine production, decreasing harmful cytokines like IFN-γ and TNF-α, while increasing IL-4 and reducing overall T-cell activity.
- The hormone's effects are dose-dependent and appear to operate through a membrane receptor, providing insights into the immune adaptations during pregnancy and potential applications for progesterone therapy in high-risk pregnancies.
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- Chemokines influence the movement of blood cells, which is crucial in various immune diseases, notably in acute and chronic graft-versus-host disease (GVHD).
- In chronic GVHD of the skin, levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) were significantly higher in patients, while there was a notable drop in certain T cells (CD4(+) expressing CXCR3) in their blood.
- The increase in CXCL10 seen in acute GVHD evolves in chronic cases, leading to the recruitment of CD4(+) T cells instead, highlighting the important role of specific chemokines in this disease's pathology.
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- Early-life colonization by intestinal microbiota shapes the developing immune system, influencing future immune responses.
- Research using neonatal animals, particularly inbred piglets, helps uncover how microbiota affects immune development and informs potential therapies.
- The study finds that colonization with specific microbiota leads to the growth of certain immune cells, particularly SIRPα(+) antigen-presenting cells, which play a key role in early mucosal immunity without affecting other immune cell types.
Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus.
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- Early-life environmental variations in mammals, particularly in piglets, can influence immune development and the risk of allergies, with farm exposure showing a protective effect against allergies.
- The study compared piglets raised in farm environments to those reared in isolation, finding differences in T-cell populations and immune responses to food proteins.
- Results indicated that farm-reared piglets had a healthier balance of regulatory and effector T-cells, suggesting that early environmental factors significantly shape the immune system's response to dietary proteins at weaning, making piglets a useful model for human studies.
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- Current understanding of lymphocyte migration suggests that naïve lymphocytes move between blood and lymph nodes but don't reach non-lymphoid tissues.
- Research showed many B lymphocytes in peripheral areas resemble naïve B cells and are found within tissues rather than near blood vessels.
- Findings indicate that naïve B cells not only exist but may also migrate in non-lymphoid organs, challenging existing views on their role in immune response and tolerance.
Absence of lymph nodes in nonmammalian species, expression of MHCII by APCs in the periphery, and the recent findings that T cells can change their polarization status after presentation in the lymph nodes imply a role for MHCII-mediated presentation outside the organized lymphoid tissue. This study shows that MHCII(+) ECs and DCs from the intestinal mucosa of the pig can present antigen to T cells in vitro. In vivo, APCs colocalize with T cells in pig and mouse intestinal mucosa.
View Article and Find Full Text PDFImmunologic response of the laryngeal mucosa to extraesophageal reflux.
Ann Otol Rhinol Laryngol
December 2008
Objectives: Extraesophageal reflux is common. The treatment costs are high, and there are associations with other diseases, including laryngeal cancer. Our studies of the mucosal immune response to this common inflammatory disease suggest an important role for the nonclassic antigen-presenting molecule CD1d in the response to inflammation.
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- Laryngopharyngeal reflux (LPR) affects a significant portion of the Western population, leading to high treatment costs and potential associations with serious diseases like laryngeal cancer, but there has been little research on its mucosal immune response.
- A study was conducted comparing laryngeal biopsies from LPR patients to control subjects, using advanced immunofluorescence techniques to analyze various immune cell markers.
- Results showed an increase in mucosal CD8(+) cells and higher expression of the nonclassical MHC molecule CD1d in patients with LPR, suggesting that the CD1d-NKT cell interaction plays a crucial role in the immune response to this condition, potentially offering new avenues for