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Antigen Specific (antigen + specific)

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Life Sciences	75%

Selected Abstracts

Treatment of autoimmune ovarian disease by co-administration with mouse zona pellucida protein 3 and DNA vaccine through induction of adaptive regulatory T cells

THE JOURNAL OF GENE MEDICINE, Issue 7 2008
Jinyao Li
Abstract Background Autoimmune ovarian disease (AOD) caused by auto-reactive T cells is considered a major reason for human premature ovarian failure, which affects 5% of women worldwide. Methods and Results To develop an effective treatment for AOD, we showed that the co-administration of mouse zona pellucida protein 3 (mZP3) protein and DNA vaccine encoding the mZP3 was able to meliorate AOD in an AOD murine model induced by the mZP3. We observed that established AOD in mice reverted to a normal ovarian morphology without notable T-cell infiltration in the co-administrated group; whereas mice in the control groups developed severe AOD. The amelioration appears to be antigen specific because other co-administration combinations failed to reverse AOD and correlates with significant reductions of pathogenic T-cell responses and productions of tumor necrosis factor-, and interferon-,. Furthermore, the melioration is apparently associated with the induction of mZP3 specific regulatory T cells that exhibit a phenotypic CD4+CD25,FoxP3+IL-10+ in the co-administrated group, which can be transferred to reverse AOD in vivo. Conclusions Thus, co-administration of mZP3 DNA and protein vaccines can be used to treat established AOD, and may provide a novel immunotherapy strategy to treat other autoimmune diseases. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Transplantation of bone marrow genetically engineered to express proinsulin II protects against autoimmune insulitis in NOD mice

THE JOURNAL OF GENE MEDICINE, Issue 11 2006
James Chan
Abstract Background Type 1 diabetes (T1D) is a T-cell-dependent autoimmune disease resulting from destructive inflammation (insulitis) of the insulin-producing pancreatic ,-cells. Transgenic expression of proinsulin II by a MHC class II promoter or transfer of bone marrow from these transgenic mice protects NOD mice from insulitis and diabetes. We assessed the feasibility of gene therapy in the NOD mouse as an approach to treat T1D by ex vivo genetic manipulation of normal hematopoietic stem cells (HSCs) with proinsulin II followed by transfer to recipient mice. Methods HSCs were isolated from 6,8-week-old NOD female mice and transduced in vitro with retrovirus encoding enhanced green fluorescent protein (EGFP) and either proinsulin II or control autoantigen. Additional control groups included mice transferred with non-manipulated bone marrow and mice which did not receive bone marrow transfer. EGFP-sorted or non-sorted HSCs were transferred into pre-conditioned 3,4-week-old female NOD mice and insulitis was assessed 8 weeks post-transfer. Results Chimerism was established in all major lymphoid tissues, ranging from 5,15% in non-sorted bone marrow transplants to 20,45% in EGFP-sorted bone marrow transplants. The incidence and degree of insulitis was significantly reduced in mice receiving proinsulin II bone marrow compared to controls. However, the incidence of sialitis in mice receiving proinsulin II bone marrow and control mice was not altered, indicating protection from insulitis was antigen specific. Conclusions We show for the first time that ex vivo genetic manipulation of HSCs to express proinsulin II followed by transplantation to NOD mice can establish molecular chimerism and protect from destructive insulitis in an antigen-specific manner. Copyright © 2006 John Wiley & Sons, Ltd. [source]

T cell receptor usage in patients with non-progressing HIV infection

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2002
M. D. BODMAN-SMITH
SUMMARY It is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long-term non-progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV-LTNP population (P < 0·05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu-lation. At follow up (1,2 years later), those patients in which CD4 levels were below 500 × 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (,,) T cell receptor and CD8 were also seen in the HIV-LTNP patients compared with controls (P = 0·002). The increase in CD8+ T cells in the HIV-LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in ,,T cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection. [source]

Efficacy of doublecortin as a marker to analyse the absolute number anddendritic growth of newly generated neurons in the adult dentate gyrus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004
Muddanna S. Rao
Abstract Doublecortin (DCX), a microtubule-associated phosphoprotein, has been recently utilized as a marker of newly born neurons in the adult dentate gyrus (DG). Nonetheless, it is unknown whether DCX exclusively labels newly formed neurons, as certain granule cells with the phenotype of differentiated neurons express DCX. We addressed the authenticity of DCX as a marker of new neurons in the adult DG by quantifying cells that are positive for 5,-bromodeoxyuridine (BrdU), DCX and both BrdU and DCX in hippocampal tissues of adult rats treated with daily injections of BrdU for 12 consecutive days. We provide new evidence that neurons visualized with DCX immunostaining in the adult rat DG are new neurons that are predominantly born during the 12 days before euthanasia. This is confirmed by the robust expression of BrdU in 90% of DCX-positive neurons in the DG of animals injected with BrdU for 12 days. Furthermore, DCX expression is specific to newly generated healthy neurons, as virtually all DCX-positive cells express early neuronal antigens but lack antigens specific to glia, undifferentiated cells or apoptotic cells. As DCX expression is also robust in the dendrites, DCX immunocytochemistry of thicker sections facilitates quantification of the dendritic growth in newly born neurons. Thus, both absolute number and dendritic growth of new neurons that are generated in the adult DG over a 12-day period can be quantified reliably with DCX immunostaining. This could be particularly useful for analysing changes in dentate neurogenesis in human hippocampal tissues as a function of ageing or neurodegenerative diseases. [source]