CD3+CD4−CD8− (double negative) T cells: Saviours or villains of the immune response?

D’Acquisto, Fulvio; Crompton, Tessa

doi:10.1016/j.bcp.2011.05.019

Cited by 158 publications

(140 citation statements)

References 93 publications

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“…Thus, in the absence of the cognate Ag or at the lowest doses tested, monoclonal OT-II thymocytes developed normally into SP4 cells. However, as the Ag concentration increased (as a surrogate for increased avidity), there was a reduction and then total elimination of OT-II SP4 cells, with a concomitant appearance of mature OT-II DN (51,52) and SP8 cells. These mature OT-II DN and SP8 cells express a TCR complex with nonmatching TCR restriction and coreceptor, because OT-II TCR is MHCII restricted.…”

Section: Discussionmentioning

confidence: 99%

Analysis of APC Types Involved in CD4 Tolerance and Regulatory T Cell Generation Using Reaggregated Thymic Organ Cultures

Guerri

Péguillet

Geraldo

et al. 2013

The Journal of Immunology

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Tolerance to self-Ags is generated in the thymus. Both epithelial and hematopoietic thymic stromal cells play an active and essential role in this process. However, the role of each of the various stromal cell types remains unresolved. To our knowledge, we describe the first comparative analysis of several types of thymic hematopoietic stromal cells (THSCs) for their ability to induce CD4 tolerance to self, in parallel with the thymic epithelium. The THSCs—two types of conventional dendritic cells (cDCs), plasmacytoid dendritic cells, macrophages (MΦs), B lymphocytes, and eosinophils—were first characterized and quantified in adult mouse thymus. They were then examined in reaggregated thymic organ cultures containing mixtures of monoclonal and polyclonal thymocytes. This thymocyte mixture allows for the analysis of Ag-specific events while avoiding the extreme skewing frequently seen in purely monoclonal systems. Our data indicate that thymic epithelium alone is capable of promoting self-tolerance by eliminating autoreactive CD4 single-positive thymocytes and by supporting regulatory T cell (Treg) development. We also show that both non-Treg CD4 single-positive thymocytes and Tregs are efficiently deleted by the two populations of cDCs present in the thymus, as well as to a lesser extent by MΦs. Plasmacytoid dendritic cells, B lymphocytes, and eosinophils were not able to do so. Finally, cDCs were also the most efficient THSCs at supporting Treg development in the thymus, suggesting that although they may share some characteristics required for negative selection with MΦs, they do not share those required for the support of Treg development, making cDCs a unique cell subset in the thymus.

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Section: Discussionmentioning

confidence: 99%

Analysis of APC Types Involved in CD4 Tolerance and Regulatory T Cell Generation Using Reaggregated Thymic Organ Cultures

Guerri

Péguillet

Geraldo

et al. 2013

The Journal of Immunology

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“…Th is type of cells is considered a major responding T cell subset in lungs of mice infected by various viruses or intracellular bacteria. Th ey are also more rapid and eff ective producers of IL-17 in early stages of infection than CD4 + T cells (Cowley et al, 2010;Lin et al, 2009;D'Acquisto and Crompton, 2011).…”

Section: Discussionmentioning

confidence: 99%

Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense

Ančicová¹,

Wagnerová²,

Janulíková³

et al. 2015

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Summary. -We have studied the impact of simultaneous infection of mice with murine gammaherpesvirus (MHV) and infl uenza A virus (IAV) on the immune response and pathogenesis of both infections. Aft er a persistent MHV-68 herpesviral infection had been established, the same mice were super-infected with IAV. Individual parameters of MHV infection (viral DNA detection in organs and blood) and numbers of leukocytes in lungs and spleens were determined. With regard to the assumed reactivation of MHV-68 (mainly in lungs, spleen, thymus and peritoneal exudate cells) we focused our attention on the detection of transcripts, typical either for lytic infection (ORF50) and/or for latency (ORF73). Herpesviral DNA was detected in above mentioned organs in several intervals during the acute phase of IAV co-infection, but the expression of monitored transcripts was lower, i.e. it has decreased. Th ough the reason for such limited expression during acute infl uenza superinfection remains unclear, it is unambiguous that lower MHV-68 expression was detected in lungs and peritoneal exudate cells (PECs) from 3 rd to 10 th day aft er co-infection with IAV. Furthermore, our study showed that the ongoing gammaherpesvirus latency in co-infected mice aff ected the number of cytotoxic T-lymphocytes and neutrophils during the acute IAV infection and lowered their deviations from that of non-infected mice. Th erefore, we suppose that co-infection with herpes and infl uenza viruses could be mutually benefi cial for the host by promoting its defense against both viruses.

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“…− doublenegative T cells and γδ T cells have both innate and adaptive characteristics and contribute significantly to the development and establishment of acute and chronic inflammatory diseases [35]. In fact, there is an expanded population of double-negative T cells and/or γδ T cells in patients with autoimmune diseases.…”

Section: T Cells But Not Cd4mentioning

confidence: 99%

“…In fact, there is an expanded population of double-negative T cells and/or γδ T cells in patients with autoimmune diseases. These cells are associated with the pathogenesis of disease by producing cytokines such as IFN-γ and IL-17 and promoting inflammation [35][36][37][38]. Such expansion of double-negative T cells and/or γδ T cells are also reported in several autoimmune-prone and -induced mouse models, including those of autoimmune encephalitis, Murphy Roths large (MRL)-lpr/lpr, BXSB, non-obese diabetic (NOD) and New Zealand black/white (NZB/W) F1 mice [36,39].…”

Section: T Cells But Not Cd4mentioning

confidence: 99%

Innate immunity drives xenobiotic-induced murine autoimmune cholangitis

Chang

Chen

et al. 2014

Clinical and Experimental Immunology

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SummaryAlthough primary biliary cirrhosis (PBC) is considered a model autoimmune disease, it has not responded therapeutically to traditional immunosuppressive agents. In addition, PBC may recur following liver transplantation, despite the absence of major histocompatibility complex (MHC) matching, in sharp contrast to the well-known paradigm of MHC restriction. We have suggested previously that invariant natural killer T (iNK T) cells are critical to the initiation of PBC. In this study we have taken advantage of our ability to induce autoimmune cholangitis with 2-octynoic acid, a common component of cosmetics, conjugated to bovine serum albumin (2-OA-BSA), and studied the natural history of pathology in mice genetically deleted for CD4 or CD8 following immunization with 2-OA-BSA in the presence or absence of α-galactosylceramide (α-GalCer). In particular, we address whether autoimmune cholangitis can be induced in the absence of traditional CD4 and CD8 responses. We report herein that CD4 and CD8 knock-out mice immunized with 2-OA-BSA/PBS or 2-OA-BSA/α-GalCer develop anti-mitochondrial antibodies (AMAs), portal infiltrates and fibrosis. Indeed, our data suggest that the innate immunity is critical for immunopathology and that the pathology is exacerbated in the presence of α-GalCer. In conclusion, these data provide not only an explanation for the recurrence of PBC following liver transplantation in the absence of MHC compatibility, but also suggest that effective therapies for PBC must include blocking of both innate and adaptive pathways.

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CD3+CD4−CD8− (double negative) T cells: Saviours or villains of the immune response?

Cited by 158 publications

References 93 publications

Analysis of APC Types Involved in CD4 Tolerance and Regulatory T Cell Generation Using Reaggregated Thymic Organ Cultures

Analysis of APC Types Involved in CD4 Tolerance and Regulatory T Cell Generation Using Reaggregated Thymic Organ Cultures

Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense

Innate immunity drives xenobiotic-induced murine autoimmune cholangitis

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