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1.
PLoS Pathog ; 19(1): e1010351, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689486

RESUMO

CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed 'memory inflation.' Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of ß2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.


Assuntos
Infecções por Citomegalovirus , Infecção Latente , Muromegalovirus , Animais , Camundongos , Células Endoteliais , Linfócitos T CD8-Positivos , Antígenos , Memória Imunológica
2.
Oecologia ; 176(3): 811-24, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25173086

RESUMO

Both plant competition and plant defense affect biodiversity and food web dynamics and are central themes in ecology research. The evolutionary pressures determining plant allocation toward defense or competition are not well understood. According to the growth-differentiation balance hypothesis (GDB), the relative importance of herbivory and competition have led to the evolution of plant allocation patterns, with herbivore pressure leading to increased differentiated tissues (defensive traits), and competition pressure leading to resource investment towards cellular division and elongation (growth-related traits). Here, we tested the GDB hypothesis by assessing the competitive response of lima bean (Phaseolus lunatus) plants with quantitatively different levels of cyanogenesis-a constitutive direct, nitrogen-based defense against herbivores. We used high (HC) and low cyanogenic (LC) genotypes in different competition treatments (intra-genotypic, inter-genotypic, interspecific), and in the presence or absence of insect herbivores (Mexican bean beetle, Epilachna varivestis) to quantify vegetative and generative plant parameters (above and belowground biomass as well as seed production). Highly defended HC-plants had significantly lower aboveground biomass and seed production than LC-plants when grown in the absence of herbivores implying significant intrinsic costs of plant cyanogenesis. However, the reduced performance of HC- compared to LC-plants was mitigated in the presence of herbivores. The two plant genotypes exhibited fundamentally different responses to various stresses (competition, herbivory). Our study supports the GDB hypothesis by demonstrating that competition and herbivory affect different plant genotypes differentially and contributes to understanding the causes of variation in defense within a single plant species.


Assuntos
Besouros/fisiologia , Herbivoria , Phaseolus/crescimento & desenvolvimento , Phaseolus/metabolismo , Animais , Evolução Biológica , Cadeia Alimentar , Genótipo , Phaseolus/genética
3.
J Exp Med ; 214(7): 1889-1899, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28566275

RESUMO

Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. The protective vaccine elicited unconventional CD8 T cell responses that were entirely restricted by MHC II or the nonclassical MHC I molecule, MHC-E. These unconventional responses were only elicited by a fibroblast-adapted rhesus CMV vector with limited tissue tropism; a repaired vector with normal tropism elicited conventional responses. Testing whether these unusual protective CD8 T responses could be elicited in humans requires vaccinating human subjects with a fibroblast-adapted mutant of human CMV (HCMV). In this study, we describe the CD8 T cell responses of human subjects vaccinated with two fibroblast-adapted HCMV vaccines. Most responses were identified as conventional classically MHC I restricted, and we found no evidence for MHC II or HLA-E restriction. These results indicate that fibroblast adaptation alone is unlikely to explain the unconventional responses observed in macaques.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Vacinas contra Citomegalovirus/imunologia , Citomegalovirus/imunologia , Fibroblastos/imunologia , Sequência de Aminoácidos , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Vacinas contra Citomegalovirus/administração & dosagem , Vacinas contra Citomegalovirus/genética , Epitopos/imunologia , Fibroblastos/virologia , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/imunologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Células K562 , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Masculino , Microscopia de Fluorescência , Mutação , Vacinação
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