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1.
Trends Immunol ; 41(3): 225-239, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32057705

RESUMO

The fetal immune system develops in a rather sterile environment relative to the outside world and, therefore, lacks antigenic education. Soon after birth, the newborn is exposed to the hostile environment of pathogens. Recently, animal- and limited human-based studies have indicated that help from the mother, upon transfer of leukocytes and their products via breast milk feeding, greatly assists the newborn's immune system. Here, I discuss the newest advances on how milk leukocytes impact early life immunity, with an emphasis on the development of the infant T cell repertoire and early immune responses in the periphery and gut-associated lymphoid tissue. A deeper understanding of these novel mechanistic insights may inform potential translational approaches to improving immunity in infants.


Assuntos
Aleitamento Materno , Leucócitos , Leite Humano , Animais , Humanos , Imunidade nas Mucosas/imunologia , Mucosa Intestinal/imunologia , Leucócitos/imunologia , Tecido Linfoide/imunologia , Leite Humano/imunologia
2.
Cell ; 134(4): 577-86, 2008 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-18691745

RESUMO

Evaluation of the therapeutic potential of RNAi for HIV infection has been hampered by the challenges of siRNA delivery and lack of suitable animal models. Using a delivery method for T cells, we show that siRNA treatment can dramatically suppress HIV infection. A CD7-specific single-chain antibody was conjugated to oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2rgamma-/- mice reconstituted with human lymphocytes (Hu-PBL) or CD34+ hematopoietic stem cells (Hu-HSC). In HIV-infected Hu-PBL mice, treatment with anti-CCR5 (viral coreceptor) and antiviral siRNAs complexed to scFvCD7-9R controlled viral replication and prevented the disease-associated CD4 T cell loss. This treatment also suppressed endogenous virus and restored CD4 T cell counts in mice reconstituted with HIV+ peripheral blood mononuclear cells. Moreover, scFvCD7-9R could deliver antiviral siRNAs to naive T cells in Hu-HSC mice and effectively suppress viremia in infected mice. Thus, siRNA therapy for HIV infection appears to be feasible in a preclinical animal model.


Assuntos
Infecções por HIV/genética , Infecções por HIV/terapia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Linfócitos T/metabolismo , Animais , Antígenos CD7/metabolismo , Modelos Animais de Doenças , Expressão Gênica , HIV-1/genética , HIV-1/metabolismo , Humanos , Fragmentos de Imunoglobulinas/metabolismo , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Viral/metabolismo
3.
Gut ; 67(5): 847-859, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28341747

RESUMO

BACKGROUND: Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. AIM: We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. METHODS: Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium. RESULTS: SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. CONCLUSIONS: SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas/fisiologia , Mucosa Intestinal/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Animais , Citometria de Fluxo , Vida Livre de Germes , Humanos , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Simbiose
4.
bioRxiv ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38659946

RESUMO

In an era where the established lines between cell identities are blurred by intra-lineage plasticity, distinguishing between stable and transitional states becomes imperative. This challenge is particularly pronounced within the Group 1 ILC lineage, where the similarity and plasticity between NK cells and ILC1s obscure their classification and the assignment of their unique contributions to immune regulation. This study exploits the unique property of Asialo-GM1 (AsGM1)-a membrane lipid associated with cytotoxic attributes absent in ILC1s-as a definitive criterion to distinguish between these cells. By prioritizing cytotoxic potential as the cardinal differentiator, our strategic use of the AsGM1 signature achieved precise delineation of NK cells and ILC1s across tissues, validated by RNA-seq analysis. This capability extends beyond steady-state classifications, adeptly capturing the binary classification of NK cells and ILC1s during acute liver injury. By leveraging two established models of NK-to-ILC1 plasticity driven by TGFß and Toxoplasma gondii , we demonstrate the stability of the AsGM1 signature, which sharply contrasts with the loss of Eomes. This signature identified a spectrum of known and novel NK cell derivatives-ILC1-like entities that bridge traditional binary classifications in aging and infection. The early detection of the AsGM1 signature at the immature NK (iNK) stage, preceding Eomes, and its stability, unaffected by transcriptional reprogramming that typically alters Eomes, position AsGM1 as a unique, site-agnostic marker for fate mapping NK-to-ILC1 plasticity. This provides a powerful tool to explore the expanding heterogeneity within the Group 1 ILC landscape, effectively transcending the ambiguity inherent to the NK-to-ILC1 continuum.

5.
J Immunol ; 185(2): 1295-302, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20548030

RESUMO

Individuals with atopic dermatitis immunized with the small pox vaccine, vaccinia virus (VV), are susceptible to eczema vaccinatum (EV), a potentially fatal disseminated infection. Dysfunction of Forkhead box P3 (FoxP3)-positive regulatory T cells (Treg) has been implicated in the pathogenesis of atopic dermatitis. To test whether Treg deficiency predisposes to EV, we percutaneously VV infected FoxP3-deficient (FoxP3(KO)) mice, which completely lack FoxP3(+) Treg. These animals generated both fewer VV-specific CD8(+) effector T cells and IFN-gamma-producing CD8(+) T cells than controls, had higher viral loads, and exhibited abnormal Th2-polarized responses to the virus. To focus on the consequences of Treg deficiency confined to the skin, we generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in which skin, but not other tissues or central lymphoid organs, lack Treg. Like FoxP3(KO) mice, the chimeras had impaired VV-specific effector T cell responses and higher viral loads. Skin cytokine expression was significantly altered in infected chimeras compared with controls. Levels of the antiviral cytokines, type I and II IFNs and IL-12, were reduced, whereas expression of the proinflammatory cytokines, IL-6, IL-10, TGF-beta, and IL-23, was increased. Importantly, infection of CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune responses comparable to controls. Our findings implicate allergic skin inflammation resulting from local Treg deficiency in the pathogenesis of EV.


Assuntos
Dermatite Atópica/imunologia , Erupção Variceliforme de Kaposi/imunologia , Linfócitos T Reguladores/imunologia , Vaccinia virus/imunologia , Animais , Transplante de Medula Óssea , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Genoma Viral/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase , Receptores CCR4/genética , Receptores CCR4/imunologia , Pele/imunologia , Pele/patologia , Pele/virologia , Baço/imunologia , Baço/metabolismo , Baço/patologia , Linfócitos T Reguladores/metabolismo , Quimeras de Transplante/sangue , Quimeras de Transplante/imunologia , Vacínia/imunologia , Vaccinia virus/genética
6.
J Immunol ; 183(1): 270-6, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19525396

RESUMO

The pathogenesis of human inflammatory bowel disease (IBD) and most experimental models of IBD is dependent on the activation and expansion of CD4(+) T cells via interaction with mucosal APCs. The costimulatory receptor CD70 is transiently expressed on the surface of conventional dendritic cells, but is constitutively expressed by a unique APC population in the intestinal lamina propria. We used two experimental IBD models to evaluate whether interfering the interaction between CD70 and its T cell ligand CD27 would affect the development of colitis. Adoptive transfer of naive CD27-deficient CD45RB(high) CD4(+) T cells into Rag-1(-/-) mice resulted in significantly less disease than when wild-type CD45RB(high)CD4(+) T cells were used. Moreover, a monoclonal anti-CD70 Ab prevented the disease caused by the transfer of wild-type CD45RB(high) CD4(+) T cells into Rag-1(-/-) mice and the same Ab also ameliorated an established disease. The colitis associated proinflammatory cytokines IL-6, TNF-alpha and IFN-gamma were significantly reduced after anti-CD70 Ab treatment, suggesting an overall reduction in inflammation due to blockade of pathogenic T cell expansion. Anti-CD70 Ab treatment also suppressed trinitrobenzene sulfonic acid-induced colitis in SJL/J mice. Because anti-CD70 Ab treatment suppressed multiple proinflammatory cytokines, this may be a more potent therapeutic approach for IBD than blockade of individual cytokines.


Assuntos
Ligante CD27/antagonistas & inibidores , Ligante CD27/fisiologia , Colite/imunologia , Colite/prevenção & controle , Transdução de Sinais/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidores , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/fisiologia , Transferência Adotiva , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Ligante CD27/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/transplante , Movimento Celular/imunologia , Colite/genética , Colite/patologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Modelos Animais de Doenças , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/fisiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/genética , Ácido Trinitrobenzenossulfônico/toxicidade , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
7.
J Allergy Clin Immunol ; 120(6): 1382-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17889291

RESUMO

BACKGROUND: Patients with atopic dermatitis (AD) exposed to the vaccinia virus (VV) smallpox vaccine have an increased risk of developing eczema vaccinatum. OBJECTIVE: To investigate the effects of local allergic skin inflammation on vaccinia immunity. METHODS: BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) to induce allergic skin inflammation or with saline control, then inoculated with an attenuated VV strain by skin scarification or intraperitoneally. After 8 days, serum IgG anti-VV and cytokine secretion by splenocytes were measured. RESULTS: Mice inoculated with VV at sites of epicutaneous sensitization with OVA, but not control mice inoculated at saline exposed sites, developed satellite pox lesions and had impaired secretion of T(H)1 cytokines in response to VV, decreased VV specific serum IgG(2a), increased VV specific serum IgG(1), and impaired upregulation of IFN-alpha, but not the cathelicidin-related antimicrobial peptide, at the infection site. The VV immune response of OVA-sensitized mice inoculated with VV at distant skin sites or intraperitoneally was normal. CONCLUSION: Local immune dysregulation at sites of allergic skin inflammation underlies the impaired T(H)1 immune response to VV introduced at these sites and the increased susceptibility to develop satellite pox lesions, a characteristic of eczema vaccinatum in patients with AD. CLINICAL IMPLICATIONS: In a mouse model of AD, inoculation of VV at inflamed skin sites is associated with increased numbers of satellite pox lesions and an abnormal immune response to the virus. This may contribute to the susceptibility of patients with AD to virus dissemination after smallpox vaccination.


Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/virologia , Vaccinia virus/imunologia , Vacínia/imunologia , Animais , Dermatite Atópica/complicações , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/virologia , Feminino , Erupção Variceliforme de Kaposi/imunologia , Erupção Variceliforme de Kaposi/virologia , Camundongos , Camundongos Endogâmicos BALB C , Vacínia/virologia
8.
PLoS One ; 11(6): e0156762, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27285085

RESUMO

Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4ß7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.


Assuntos
Quimiotaxia de Leucócito , Imunidade Materno-Adquirida/imunologia , Imunização Passiva , Lactação/imunologia , Leite/imunologia , Nódulos Linfáticos Agregados/imunologia , Linfócitos T Citotóxicos/fisiologia , Animais , Animais Recém-Nascidos , Animais Lactentes , Células Cultivadas , Quimiotaxia de Leucócito/fisiologia , Feminino , Imunização Passiva/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Leite/citologia , Mães , Nódulos Linfáticos Agregados/citologia , Linfócitos T Citotóxicos/citologia
9.
Sci Rep ; 5: 12113, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26178856

RESUMO

The transcription factor PLZF (promyelocytic leukemia zinc finger; zbtb16) is essential for nearly all of the unique characteristics of NKT cells including their rapid and potent response to antigen. In the immune system, zbtb16 expression is only found in innate cells. Conventional T cells that ectopically express PLZF spontaneously acquire an activated, effector phenotype. Activation induced expression of lineage defining transcription factors such as T-bet, FoxP3, RORγt, GATA3 and others is essential for naïve T cell differentiation into effector T cells. In this study, we used sensitive genetic-based approaches to assess the induction of PLZF expression in non-innate T cells by T cell receptor (TCR)-mediated activation. Surprisingly, we found that PLZF was stably repressed in non-innate T cells and that TCR-mediated signaling was not sufficient to induce PLZF in conventional T cells. The inactivated state of PLZF was stably maintained in mature T cells, even under inflammatory conditions imposed by bacterial infection. Collectively, our data show that, in contrast to multiple recent reports, PLZF expression is highly specific to innate T cells and cannot be induced in conventional T cells via TCR-mediated activation or inflammatory challenge.


Assuntos
Fatores de Transcrição Kruppel-Like/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Animais , Camundongos , Proteína com Dedos de Zinco da Leucemia Promielocítica , Timo/citologia , Timo/metabolismo
10.
BMJ Open Gastroenterol ; 1(1): e000009, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26462264

RESUMO

INTRODUCTION AND OBJECTIVE: The role of secreted gut microbial components in the initiation of systemic inflammation and consequences of antibiotic therapies on this inflammatory process are poorly elucidated. We investigate whether peripheral innate cells mount an inflammatory response to gut microbial components, the immune cells that are the primary drivers of systemic inflammation, the bacterial populations that are predominantly responsible, and whether perioperative antibiotics affect these processes. METHOD AND EXPERIMENTAL DESIGN: Conditioned supernatants from gut microbes were used to stimulate murine innate cell types in vitro and in vivo, and proinflammatory responses were characterised. Effects of antibiotic therapies on these responses were investigated using a model of experimental intestinal barrier damage induced by dextran sodium sulfate. RESULTS: Proinflammatory responses in the periphery are generated by components of anaerobes from the Bacteroidetes phylotype and these responses are primarily produced by myeloid dendritic cells. We found that the common prophylactic therapy for sepsis (oral neomycin and metronidazole administered to patients the day prior to surgery) is ineffective for clearing Bacteroidetes from the murine intestine. A point of critical consequence of this result is the increased systemic inflammation and premature death observed in treated mice, and these outcomes appear to be independent of gut bacterial spread in the initial phase of intestinal barrier damage. Importantly, spillage of gut microbial products, rather than dissemination of gut microbes, may underlay the initiation of systemic inflammation leading to death. CONCLUSIONS: Our data further affirm the importance of a balanced gut microflora biodiversity in host immune homeostasis and reinforce the notion that inadequate antibiotic therapy can have detrimental effects on overall immune system.

11.
PLoS One ; 3(12): e4089, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19116651

RESUMO

It is generally thought that during the contraction phase of an acute anti-viral T cell reponse, the effector T cells that escape activation-induced cell death eventually differentiate into central memory T cells over the next several weeks. Here we report that antigen-specific CD8T cells with the phenotype and function of central memory cells develop concomitantly with effector T cells during vaccinia virus (vv) infection. As soon as 5 days after an intraperitoneal infection with vv, we could identify a subset of CD44(hi) and CD62L(+) vv-specific CD8 T cells in the peritoneal exudate lymphocytes. This population constituted approximately 10% of all antigen-specific T cells and like central memory T cells, they also expressed high levels of CCR7 and IL-7R but expressed little granzyme B. Importantly, upon adoptive transfer into naïve congenic hosts, CD62L(+), but not CD62L(-) CD8 T cells were able to expand and mediate a rapid recall response to a new vv challenge initiated 6 weeks after transfer, confirming that the CD62L(+) vv-specific CD8 T cells are bonafide memory cells. Our results are thus consistent with the branched differentiation model, where effector and memory cells develop simultaneously. These results are likely to have implications in the context of vaccine design, particularly those based on vaccinia virus recombinants.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Vacínia/imunologia , Animais , Selectina L/imunologia , Listeria monocytogenes/patogenicidade , Listeriose/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Vaccinia virus/imunologia , Vaccinia virus/patogenicidade
12.
J Immunol ; 178(2): 652-6, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17202324

RESUMO

NK cell receptors (NKRs) modulate T lymphocyte responses by modifying the Ag activation threshold. However, what governs their expression on T cells remains unclear. In this study we show that different NKRs are imprinted on CD8 T cells in the gut mucosa and periphery during the same Ag challenge. After a viral, bacterial, and tumor challenge, most CD8 peritoneal exudate lymphocytes expressed NKG2A but not 2B4. In contrast, most CD8 intraepithelial lymphocytes exhibited 2B4 but not NKG2A. Our data suggest that tissue-specific factors may determine the pattern of NKR expression. In the gut, CD70 licensing appears to promote 2B4 induction on mucosal CD8 T cells. Conversely, retinoic acid produced by the intestinal dendritic cells may suppress NKG2A expression. Thus, tissue-specific factors regulate NKR expression and may confer T cells with differing effector functions in a tissue and site-specific manner.


Assuntos
Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade nas Mucosas , Células Matadoras Naturais/imunologia , Animais , Ligante CD27/imunologia , Linfócitos T CD8-Positivos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Intestinos/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mucosa/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK , Neoplasias/metabolismo , Especificidade de Órgãos/imunologia , Receptores Imunológicos/imunologia , Receptores de Células Matadoras Naturais , Tretinoína/farmacologia
13.
J Allergy Clin Immunol ; 119(3): 671-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17336617

RESUMO

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder occurring in genetically predisposed individuals with a systemic T(H)2 bias. Atopic dermatitis patients exposed to the smallpox vaccine, vaccinia virus (VV), occasionally develop eczema vaccinatum (EV), an overwhelming and potentially lethal systemic infection with VV. OBJECTIVE: To establish a murine model of EV and examine the effects of skin inflammation on VV immunity. METHODS: The skin of RelB(-/-) mice, like that of chronic AD lesions in humans, exhibits thickening, eosinophilic infiltration, hyperkeratosis, and acanthosis. RelB(-/-) and wild-type (WT) control mice were infected with VV via skin scarification. Viral spread, cytokine levels, IgG2a responses and VV-specific T cells were measured. RESULTS: Cutaneously VV-infected RelB(-/-), but not WT mice, exhibited weight loss, markedly impaired systemic clearance of the virus and increased contiguous propagation from the inoculation site. This was associated with a dramatically impaired generation of IFN-gamma-producing CD8(+) vaccinia-specific T cells along with decreased secretion of IFN-gamma by VV-stimulated splenocytes. The T(H)2 cytokines-IL-4, IL-5, IL-13, and IL-10-on the other hand, were overproduced. When infected intraperitoneally, RelB(-/-) mice generated robust T cell responses with good IFN-gamma production. CONCLUSION: Allergic inflammation in RelB(-/-) mice is associated with dysregulated immunity to VV encountered via the skin. We speculate that susceptibility of AD patients to overwhelming vaccinia virus infection is similarly related to ineffective T cell responses. CLINICAL IMPLICATIONS: The susceptibility of patients with AD to EV following cutaneous contact with VV is related to ineffective antiviral immune responses.


Assuntos
Dermatite Atópica/complicações , Erupção Variceliforme de Kaposi/imunologia , Pele/imunologia , Fator de Transcrição RelB/genética , Vaccinia virus , Animais , Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , Dermatite Atópica/genética , Imunidade/genética , Imunoglobulina G/imunologia , Erupção Variceliforme de Kaposi/genética , Camundongos , Camundongos Mutantes , Pele/virologia , Redução de Peso/genética
14.
Nat Immunol ; 6(7): 698-706, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15937486

RESUMO

One unresolved issue in gut immunity is how mucosal T lymphocytes are activated and which antigen-presenting cell (APC) is critical for the regulation of this process. We have identified a unique population of APCs that is exclusively localized in the lamina propria. These APCs constitutively expressed the costimulatory molecule CD70 and had antigen-presenting functions. After oral infection of mice with Listeria monocytogenes, proliferation and differentiation of antigen-specific T cells occurred in the gut mucosa in situ and blockade of CD70 costimulation abrogated the mucosal T cell proliferation and effector functions. Thus, a potent CD70-dependent stimulation via specialized tissue-specific APCs is required for the proliferation and differentiation of gut mucosal T cells after oral infection.


Assuntos
Antígenos CD/imunologia , Mucosa Intestinal/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Proteínas de Membrana/imunologia , Linfócitos T/imunologia , Animais , Apresentação de Antígeno/imunologia , Ligante CD27 , Diferenciação Celular/imunologia , Citometria de Fluxo , Imuno-Histoquímica , Mucosa Intestinal/citologia , Mucosa Intestinal/microbiologia , Listeriose/patologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Fagocitose/imunologia , Organismos Livres de Patógenos Específicos , Linfócitos T/citologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
15.
J Immunol ; 170(8): 4095-101, 2003 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-12682239

RESUMO

The magnitude and diversity of Ag-specific T cell effector activity have been proposed to be controlled by an integration of positive signals transduced by the TCR and negative signals originating from inhibitory cell surface molecules. Although the lectin family of NK cell-associated inhibitory receptors has been reported to regulate the function of murine CTLs, gp49B1, the Ig superfamily member is not known to be expressed on T cells. Moreover, the consequences of the lack of an endogenously expressed NK cell-associated inhibitory receptor on T cell functions are not known. We report that gp49B1 is expressed by nearly all activated CD8 and CD4 T cells in addition to NK cells during an immune response to viral, bacterial, or tumor challenge. Kinetics of gp49B1 expression parallel functional capability and subside in the memory phase. Following vaccinia viral infection, IFN-gamma production by both subsets of T cells and NK cells is enhanced in gp49B1-deficient mice compared with gp49B1(+/+) mice. The stimulation threshold for IFN-gamma production is also lower in gp49B1-deficient T cells. In contrast, no significant differences were observed in the cytotoxic responses. We conclude that gp49B1 is a unique inhibitory receptor that is induced in multiple lineages of innate and adaptive immune cells during an infection and controls their IFN-gamma, but not cytotoxic responses.


Assuntos
Interferon gama/fisiologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Glicoproteínas de Membrana/fisiologia , Receptores Imunológicos/fisiologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adjuvantes Imunológicos/biossíntese , Adjuvantes Imunológicos/deficiência , Adjuvantes Imunológicos/genética , Adjuvantes Imunológicos/fisiologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Testes Imunológicos de Citotoxicidade , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Epitopos de Linfócito T/imunologia , Memória Imunológica/genética , Interferon gama/metabolismo , Células Matadoras Naturais/virologia , Listeria monocytogenes/imunologia , Ativação Linfocitária/genética , Masculino , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores Imunológicos/biossíntese , Receptores Imunológicos/deficiência , Receptores Imunológicos/genética , Sarcoma Experimental/genética , Sarcoma Experimental/imunologia , Subpopulações de Linfócitos T/virologia , Células Tumorais Cultivadas , Vaccinia virus/imunologia
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