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1.
J Immunol ; 202(3): 653-663, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30598513

RESUMO

CD4+ T cell responses are crucial for the control of many intracellular pathogens, yet the requirements for their induction are not fully understood. To better understand the role that various dendritic cell (DC) subtypes play in CD4+ T cell priming, we compared in vivo T cell responses to skin inoculation of mice with infectious or UV-inactivated HSV type 1. Localized infection elicited a Th1 response that was primed in skin-draining lymph nodes involving Ag presentation by migratory dermal and lymph node-resident DC. However, expansion and Th1 differentiation was impaired in response to UV-inactivated virus (UV-HSV), and this defect correlated with a restriction of Ag presentation to migratory CD103- dermal DC. A similar differentiation defect was seen in infected mice lacking CD8α+ and CD103+ classical type 1 DC (cDC1). Finally, Th1 differentiation after UV-HSV inoculation was rescued by targeted Ag delivery to CD8α+ and CD103+ cDC1 using an anti-Clec9A Ab construct. This suggests that Ag presentation by cDC1 is crucial for optimal Th1 immunity to HSV type 1 infection and potentially other pathogens of the skin.


Assuntos
Apresentação de Antígeno , Células Dendríticas/imunologia , Herpes Simples/imunologia , Células de Langerhans/imunologia , Dermatopatias Virais/imunologia , Células Th1/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Feminino , Herpesvirus Humano 1/efeitos da radiação , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Raios Ultravioleta , Inativação de Vírus/efeitos da radiação
2.
Sci Rep ; 12(1): 4034, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260653

RESUMO

Natural Killer T (NKT) cells and Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells that express semi-invariant αß T cell receptors (TCRs) through which they recognise CD1d and MR1 molecules, respectively, in complex with specific ligands. These cells play important roles in health and disease in many organs, but their precise intra-organ location is not well established. Here, using CD1d and MR1 tetramer staining techniques, we describe the precise location of NKT and MAIT cells in lymphoid and peripheral organs. Within the thymus, NKT cells were concentrated in the medullary side of the corticomedullary junction. In spleen and lymph nodes, NKT cells were mainly localised within T cell zones, although following in vivo activation with the potent NKT-cell ligand α-GalCer, they expanded throughout the spleen. MAIT cells were clearly detectable in Vα19 TCR transgenic mice and were rare but detectable in lymphoid tissue of non-transgenic mice. In contrast to NKT cells, MAIT cells were more closely associated with the B cell zone and red pulp of the spleen. Accordingly, we have provided an extensive analysis of the in situ localisation of NKT and MAIT cells and suggest differences between the intra-organ location of these two cell types.


Assuntos
Tecido Linfoide , Células T Invariantes Associadas à Mucosa , Células T Matadoras Naturais , Animais , Tecido Linfoide/metabolismo , Camundongos , Camundongos Transgênicos , Células T Invariantes Associadas à Mucosa/metabolismo , Células T Matadoras Naturais/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo
3.
Science ; 367(6478)2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31919129

RESUMO

Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ chain. BTN2A1 associates with another butyrophilin, BTN3A1, and these act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This distinctive mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell-based immunotherapies.


Assuntos
Antígenos de Neoplasias/imunologia , Butirofilinas/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Antígenos CD/química , Antígenos CD/imunologia , Butirofilinas/química , Butirofilinas/genética , Linhagem Celular Tumoral , Humanos , Ligantes , Ativação Linfocitária , Fosforilação , Domínios Proteicos , Multimerização Proteica
4.
Cell Rep ; 25(1): 68-79.e4, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30282039

RESUMO

Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8+ T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8+ T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Fígado/imunologia , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/citologia , Epitopos , Hepatite/imunologia , Interleucina-15/imunologia , Fígado/citologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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