Idiotype‐pulsed dendritic cells are able to induce antitumoral cytotoxic CD8 cells in chronic lymphocytic leukaemia
Françoise VuillierKarim MaloumElaine K. ThomasChristian MagnacGérard DumasBéatrice Payelle‐BrogardPablo OppezzoGuillaume DighieroDaniel Scott‐Algara
19
Citation
35
Reference
10
Related Paper
Citation Trend
Abstract:
Summary. Idiotypic structures of immunoglobulins from malignant B cells constitute tumour‐specific antigens, though the function of immunoglobulin‐specific CD8 + T cells in disease control and rejection remains unclear. We have studied five cases of B chronic lymphocytic leukaemia patients affected with indolent (three patients) or aggressive (two patients) disease. We showed that CD8 + T cells with major histocompatibility complex class I‐restricted cytotoxicity against autologous tumour B cells could be generated following repeated stimulations with idiotype‐pulsed dendritic cells in vitro . CD8 + T‐cell lines were able to upregulate CD69 expression and to release interferon (IFN)‐γ upon contact with the autologous B cells, though cytolytic activity was only substantiated for patients with indolent disease. The failure of cytolytic activity in patients with aggressive disease may be explained by a skewed maturation of memory CD8 cells.In this report we describe a system for the generation of functional, class I MHC-restricted, T-T hybridomas. The BW5147 cell line was transfected with the CD8 gene. BW5147 transfectants were obtained that stably expressed CD8 and this expression was maintained after somatic cell hybridization with activated T lymphocytes. To determine whether the stable expression of CD8 would facilitate the generation of class I MHC-specific T-T hybridomas, the transfected cells were fused with alloreactive T cells and the resultant hybrids were screened for their ability to produce lymphokines in response to antigenic stimulation. Somatic cell hybridizations with BW5147-CD8 transfectants give rise to a much higher frequency of class I MHC-specific T-T hybridomas relative to parallel fusions with BW5147. To determine whether the BW5147-CD8 transfectants would also support the generation of Ag-specific, class I MHC-restricted T-T hybridomas, they were fused with OVA-specific CTL. Several T-T hybrid clones were identified that produced lymphokines after stimulation with a transfected APC that was synthesizing OVA, or with a tryptic digest of OVA in the presence of syngeneic APC. The stimulation by Ag was MHC-restricted and mapped to the Kb molecule. An anti-CD8 mAb inhibited the stimulation of these hybridomas by Ag plus APC, whereas their stimulation by mitogen was unaffected. Cytolytic activity was not detected when several of the OVA-specific or alloreactive hybridomas were tested for their ability to kill target cells bearing the appropriate Ag. These results demonstrate that the BW5147-CD8 transfectants allow the generation of class I MHC-restricted T-T hybridomas. The potential utility of this system is discussed.
CTL*
Cite
Citations (85)
Monocyte
Cite
Citations (19)
To explore the role of IL-22 on the recovery and function of thymus from graft-versus host disease (GVHD) mice after allogeneic bone marrow transplantation (allo-BMT).GVHD model was established by using of recipient male BALB/c and donor male C57BL/6 mice(6-8 W) respectively. The mice were divided into normal group, GVHD with IL-22 group (BS+IL-22) and without IL-22 group (BS+PBS). Numbers of thymus cells were detected at different time points. The ratio of T cell subsets from thymus was observed by flow cytometry. Percentages of IFN-γ-producing and IL-17-producing CD4+ T or CD8+ T cells were detected.The total number of thymus cells in BS+IL-22 mice [(14.6±5.1)×10⁴] was significantly higher than that in BS+PBS mice [(6.2±2.9)×10⁴] at 14 days after allo-BMT. Thymus cells in BS+IL-22 mice expanded continuously and reached at the level of normal mice, which were still higher than that in BS+PBS group. Although there was no impact on the ratio of mature CD4+ and CD8+ T cell from thymus, the percentage of immature CD4+CD8+ T cell increased obviously in mice treated with IL-22. Percentages of IFN-γ+CD4+ T cell [Th1:(2.42±0.75)%] and IFN-γ+CD8+ T cell [Tc1:(5.44±0.47)%] were up-regulated by IL-22 treatment, whereas no changes were detected in IL-17+CD4+ T cell (Th17) and IL-17+CD8+ T cell (Tc17).IL-22 accelerates the progress of thymus recovery, and increases the IFN-γ-producing ability of thymus CD4+ and CD8+ T cells from GVHD mice.
Cite
Citations (0)
Like many T cells in the myelin basic protein (MBP)-specific T-cell repertoire, CD4(-) GP2.3H3.16 (3H3) T cells recognize guinea pig MBP as an agonist but recognize autologous rat (R)MBP as a mixed agonist/antagonist. 3H3 T cells do not exhibit proliferative responses to RMBP but nonetheless respond to RMBP by accumulation of T-cell surface I-A/peptide complexes and generation of T-cell antigen-presenting cell (T-APC) activity. This study showed that presentation of RMBP by 3H3 T-APC is long-lived but is lost during interactions with cognate responders or on overt activation of T-APCs. Presentation of RMBP to encephalitogenic T cells resulted in the reciprocal activation of 3H3 T-APCs as evidenced by blastogenesis, proliferation, and induction of interleukin-2R and OX40 markers on 3H3 T-APC. These data indicate that T-APCs, like B-cell APCs, undergo clonal expansion after presentation of a cognate antigen to T-cell responders.
Cite
Citations (8)
Cite
Citations (61)
Background. The in vivo effects of immunosuppressants on T cells are classically determined using animal models of organ transplantation. These methods are technically difficult and time consuming. A simple in vivo method is needed for screening new immunosuppressants. Methods. Donor mouse spleen cells were labeled with a fluorescent dye, carboxy-fluorescein diacetate succinimidyl ester (CFSE), and then injected into the blood of recipient severe combined immunodeficiency mice. Three days after the injection, spleen cells of the recipient mice were isolated and the proliferating alloreactive T cells were analyzed by flow cytometry. Results. In control recipient mice, 50% of the T cells were proliferating, consisting of both CD4+ and CD8+ T cells. In cyclosporine- or FK506-treated mice, T-cell proliferation was suppressed in the CD4 subset but not in the CD8 subset. On the contrary, T-cell proliferation was significantly reduced in the CD8 subset but not in the CD4 subset in recipient mice treated with rapamycin. Conclusion. The present mouse model using carboxy-fluorescein diacetate succinimidyl ester labeling is simple and fast. It is useful for screening new immunosuppressants and for examining the effect on T-cell subsets.
Cite
Citations (15)
Objecfive To study T cell subsets distribution in peripheral blood from patients with ankylosing spondylitis(AS)and the role of cell immunity in AS.Methods 30 patients with untreated active phase AS and 30 healthy volunteers were enrolled.The expression of CD4+ and CD8+ T cell subsets were evaluated by flow eytome try.The correlation among T cell subsets and Bath AS function index(BASFI).Bath AS measurement index(BASMI),course of disease,age,ESR,hyper-sensitive C-reactive protein (hs-CRP) were analyzed.Results The level of CD4+ T cell and CD4/CD8+ratio were significantly lower than that of healthy volunteers[(29.24±9.22)% vs.(40.09±6.86) %,(0.96±0.49 ) vs.(1.70±0.67 ),P ＜ 0.01 ],and CD8+ T cell were significantly higher than that of healthy volunteers [(32.91±6.86) % vs.(25.60± 5.97 ) %,P ＜ 0.01 ].The level of CD4+ T cell subsets in peripheral blood of AS patients was negatively correlated with BASMI (r =-0.479,P ＜ 0.01 ),and CD8+ T cell subsets were positively correlated with ESR,hs-CRP,BASFI and BASMI ( r = 0.373,0.430,0.462,0.530,P ＜0.05 ).The ratio of CD4+/CD8+ was negatively correlated with hs-CRP,BASFI and BASMI (r = -0.465,- 0.473,- 0.426,P ＜ 0.05 ).CD4+,CD8+,ratio of CD4/CD8 were not significantly correlated with age and course of disease in patients with AS.Conclusion T cell subsets are significantly abnormal in peripheral blood of patients with AS,and the imbalance degree of T cell is correlated with severity and activity of AS,suggesting that T cell subsets imbalance plays an important role in the pathologensis of AS.
Key words:
Ankylosing spondylitis; T cell subsets; CD4+; CD8+
BASFI
Spondylitis
Cite
Citations (1)
Activation of T cells is normally promoted by interaction of T cell receptors with complexes of antigenic peptide bound to MHC (major histocompatibility complex) proteins on the surface of antigen-presenting cells (APCs). However, Ge et al. report that activation of naïve or CD8 + T cells can occur with exposure to soluble peptide-MHC complexes in the absence of APCs. Their results indicated that activation actually occurred through transfer of peptides to MHC molecules expressed by the T cells. Thus, T cells were only activated if they expressed the same MHC as the one with which they were stimulated. Furthermore T cells that had been exposed to MHC-peptide monomers and then washed could subsequently activate naïve T cells, apparently by presenting the peptide antigen on their cell surface as would a professional APC. Given that soluble peptide-MHC complexes are likely to exist in serum or synovial fluid, the authors propose that such presentation of antigen by T cells in vivo could influence T cell maturation. Q. Ge, J. D. Stone, M. T. Thompson, J. R. Cochran, M. Rushe, H. N. Eisen, J. Chen, L. J. Stern, Soluble peptide-MHC monomers cause activation of CD8 + T cells through transfer of the peptide to T cell MHC molecules. Proc. Natl. Acad. Sci. U.S.A. 99 , 13729-13734 (2002). [Abstract] [Full Text]
MHC restriction
Streptamer
Cite
Citations (0)
Objective To investigatethe effectsofShengyudecoction (SYD)onTcellsubgroupsandcytokine levels in immuno deficiency mice. Methods Kunming type mice were injected with cyclophosphamide to establish immuno deficiency mice model. The immuno deficiency mice were fed with low dose, high dose SYD respectively,once a day. On the 30th day, the mice were weighted; blood and the plasma was separated to measure the cytokine levels by ELISA test, and the T cell subgroups of CD3+, CD4+and CD8+ were measured by flow cytometor analysis system. Results Cyclophosphamide remarkedly resulted in decreasing of CD3+T cell, CD4+T cell, CD4+/CD8+ratio, IL-2 and IL-4 production. SYD could increase the percentage of CD3+T cell, CD4+T cell and CD4+/CD8+ ratio obviously in immuno deficiency mice compared to those in cyclophosphamide group (p0.05). The plasma level of IL-2 and IL-4 of immune deficit mice could be significantly improved by SYD. Conclusion SYD can immunomodulate the unusual distribution caused by cyclophosphamide among T cell subgroups of the mice with low immunity, improve the percentage of CD3+T cell, CD4+T cell and the ratio of CD4+/CD8+in mice, and promote the secretion of IL-2, IL-4 cytokines in mice with low immunity.
Cite
Citations (0)
We investigated the mechanism of T cell response to murine embryonal carcinoma F9 cells. Thy-1+, CD4-, CD8- (double-negative) cytotoxic effector cells were induced in spleen cells obtained from immune A.BY mice to F9 cells, and the cytotoxic activity was major histocompatibility complex (MHC)-unrestricted. Furthermore, CD4+ T cells were essential for the induction of double-negative cytotoxic T lymphocytes directed to F9 cells. Most of the double-negative cytotoxic T lymphocyte lines obtained by long-term culture of the effector cells had CD3 molecule and T-cell receptor beta chain on their cell surface, and the CD3 molecule was found to be involved in target cell recognition. The T cell receptor alpha beta+ double-negative cytotoxic T lymphocyte line (2A5) also lysed various tumor cells in a non-MHC-restricted manner, but did not lyse concanavalin A-stimulated blasts of 129 strain, from which F9 cells had originated. These results indicate that T cell receptor alpha beta+ double-negative cytotoxic T lymphocytes induced by F9 cells recognize a common antigen(s) expressed on F9 cells and other tumor cells but not minor histocompatibility antigens.
Lymphokine-activated killer cell
Cite
Citations (1)