Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo

Tadokoro, Carlos E.; Shakhar, Guy; Shen, Shiqian; Ding, Yi; Lino, Andreia C.; Maraver, Antonio; Lafaille, Juan J.; Dustin, Michael L.

doi:10.1084/jem.20050783

Cited by 462 publications

(383 citation statements)

References 26 publications

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“…Overall, these results show that direct contact-based interactions between T reg and T eff cells persisted with or without CD11c + DCs, which could reflect distinct subsets of T cells or distinct stages of the T cell function in the target tissues. The functional relevance of the different types of interactions has already been documented in vitro (Takahashi et al, 1998;Thornton and Shevach, 1998;Ermann et al, 2001;Nakamura et al, 2001;Piccirillo and Shevach, 2001;BaecherAllan et al, 2006;Tadokoro et al, 2006;Onishi et al, 2008;Wing et al, 2008;Hagness et al, 2012;Huang et al, 2012). Our noninvasive in vivo imaging studies shows that those The data were pooled from 6 videos from three experiments with 5 mice.…”

Section: T Reg Cells Persistently Interacted With T Eff Cells Even Whsupporting

confidence: 54%

“…Initial studies with in vitro transwell culture systems showed that T reg cell suppression was effective only if T reg cells were placed in the same culture chamber with T eff cells and antigen-presenting cells (Takahashi et al, 1998;Thornton and Shevach, 1998). Although subsequent studies showed that T reg cells could inhibit T eff cell activation by modulating antigen-presenting cells (Tadokoro et al, 2006;Onishi et al, 2008;Wing et al, 2008), several in vitro studies also demonstrated that both human and murine T reg cells could directly suppress T eff cells independent of antigen-presenting cells (Ermann et al, 2001;Nakamura et al, 2001;Piccirillo and Shevach, 2001;Baecher-Allan et al, 2006;Hagness et al, 2012;Huang et al, 2012). However, ex vivo and in vivo imaging studies in lymph nodes did not detect stable contact between T reg and T eff cells (Mempel et al, 2006;Tang et al, 2006).…”

Section: T Reg Cells Interacted With T Eff Cells Through Direct Cell-mentioning

confidence: 99%

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Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

Jason¹,

Abdulreda²,

Devarajan³

et al. 2014

J Cell Biol

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Real-time imaging studies are reshaping immunological paradigms, but a visual framework is lacking for self-antigen-specific T cells at the effector phase in target tissues. To address this issue, we conducted intravital, longitudinal imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate some key aspects of T cell biology. We used mouse models of T cell-mediated damage and protection of pancreatic islet grafts. Both CD4 + and CD8 + effector T (T eff ) lymphocytes directly engaged target cells. Strikingly, juxtaposed  cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. In target tissue, Foxp3 + regulatory T (T reg ) cells persistently contacted T eff cells with or without involvement of CD11c + dendritic cells, an observation conciliating with the in vitro "trademark" of T reg function, contact-dependent suppression. This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings.

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Section: T Reg Cells Persistently Interacted With T Eff Cells Even Whsupporting

confidence: 54%

Section: T Reg Cells Interacted With T Eff Cells Through Direct Cell-mentioning

confidence: 99%

Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

Jason¹,

Abdulreda²,

Devarajan³

et al. 2014

J Cell Biol

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“…Young BWF1 mice and nonautoimmune control mice did not show the infiltration of inflammatory cells (data not shown). Moreover, both Foxp3 ϩ and Foxp3 Ϫ CD4 ϩ T cells were apparently distributed evenly within the infiltrating site of the target organs ( Figure 3, A and C), indicating that clustering of these cells that were essential for T reg cell-mediated suppression 26,27 would take place in the target organs as well as in the lymphoid organs.…”

Section: T Reg Cells Infiltrated Into the Target Organsmentioning

confidence: 99%

“…26,27 Because our analyses on the number, function, and site of the development of T reg cells could not find any obvious defect, we examined the localization of T reg cells within the secondary lymphoid organs of BWF1 mice. T reg cells in aged BWF1 mice were located in the follicles and red pulp as well as periaortic lymphoid sheath in the spleen, whereas T reg cells in young BWF1 mice were mostly located in the periaortic lymphoid sheath ( …”

Section: Altered Distribution Of T Reg Cells Within the Secondary Lymmentioning

confidence: 99%

Increased Foxp3+ CD4+ Regulatory T Cells with Intact Suppressive Activity but Altered Cellular Localization in Murine Lupus

Abe

Ueha

Suzuki

et al. 2008

The American Journal of Pathology

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Foxp3 ؉ CD4 ؉ regulatory T (T reg ) cells play a pivotal role in the maintenance of dominant self tolerance. Understanding how the failures of immune control by T reg cells are involved in autoimmune diseases is important for the development of effective immunotherapies. In the present study, we analyzed the characteristics of endogenous T reg cells in (NZB ؋ NZW) F1 (BWF1) mice, a murine model of systemic lupus erythematosus. Unexpectedly, T reg number and frequency in aged BWF1 mice with developing lupus nephritis were increased, not decreased, and in vitro suppressive activity in lymphoid organs was intact. In addition, T reg cells trafficked to target organs because cells were present in the kidney and lung. T reg cells of aged BWF1 mice exhibited altered localization within lymph organs, however, and an altered phenotype, with higher expression levels of chemokine receptors and activation markers, suggesting a highly activated cellular state. Notably, the expression levels of costimulatory molecules were also markedly enhanced in the T reg cells of aged BWF1 mice. Furthermore, T reg cells of BWF1 mice did not show any suppressive effects on antibody production in vitro. Taken together, we conclude that T reg cells in BWF1 mice are not predisposed to functional incompetence but rather are present in a highly activated state. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology characterized by a massive production of autoantibodies against various nuclear antigens. The deposit of immune complexes in the target organs, ie, skin, kidney, lung, joints, and central nervous system, is thought to cause fatal dysfunction of the body system. (NZB ϫ NZW) F1 (BWF1) is a mouse strain that has been widely used as a model for SLE since the 1960s. These mice spontaneously develop severe autoimmune disease highly resembling human SLE in terms of serological and hematological abnormalities, and severe nephritis accompanying massive production of antinuclear antibodies. 1 Reconstitution of SCID (severe combined immunodeficiency) mice with cultured pre-B cells of BWF1 mice recapitulates many symptoms of the disease of BWF1 mice. Cultured pre-B cells alone, however, are not sufficient to fully reproduce the disease. 2 These data suggest that cellular subset(s) in addition to B cells are necessary for the development of the lupus-like syndrome of BWF1 mice, although abnormalities of the immune system predominantly lie within B cells. One of the possible candidates is CD4 ϩ T cells, because depletion of CD4 ϩ T cells with anti-CD4 antibody from 5 months old, slightly before the disease onset, prevents the development of the disease. 3,4 CD4 ϩ T cells are, therefore, also required for the development of the disease in BWF1 mice, possibly by providing help for the production of high-affinity autoantibodies.Studies in this decade have clearly shown the key roles of naturally occurring regulatory T (T reg ) cells in the maintenance of dominant self tolerance of the immune system. 5 T reg cells in normal mi...

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“…Shortly after this, the Wrst papers investigating cell migration in explanted lymph nodes or thymic stromal reaggregate cultures (Bousso et al 2002) were published, followed by true intravital studies (Gunzer et al 2004;Mempel et al 2004). Meanwhile the number of reports using intravital 2PM for immunological questions has risen enormously, spanning from the cellular events of T cell activation (Miller et al 2004a), formation and function of germinal centers (Allen et al 2007b;Schwickert et al 2007) or function of regulatory T cells (Tadokoro et al 2006) to complex processes such as granuloma formation ) and the delivery of antigens (Carrasco and Batista. 2007;Qi et al 2006) or viruses to B cells (Junt et al 2007a).…”

Section: Analysis Of Cell Migration In Vivomentioning

confidence: 99%

3D and 4D imaging of immune cells in vitro and in vivo

Nitschke

Garin

Kosco‐Vilbois

et al. 2008

Histochem Cell Biol

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Analyzing the dynamics of cellular immune responses, although performed for decades in immunologic research, has seen an enormous increase in the number of studies using this approach since the development of intravital 2-photon microscopy. Meanwhile, new insights into the dynamics of cellular immunity are being published on a daily basis. This review gives a short overview of the currently most widely used techniques, both on the microscopy side as well as on the experimental part. DiYculties and promises will be discussed. Finally, a personal selection of the most interesting Wndings of the Wrst 6 years of intravital 2-photon microscopy for immunological questions will be given. The overall aim is to get the reader interested into this fascinating way of investigating the immune response by means of "dynamic histology". This already has and will continue to broaden our view on how immune cells work in real life.

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Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo

Cited by 462 publications

References 26 publications

Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

Increased Foxp3+ CD4+ Regulatory T Cells with Intact Suppressive Activity but Altered Cellular Localization in Murine Lupus

3D and 4D imaging of immune cells in vitro and in vivo

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