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1.
Sci Rep ; 12(1): 19487, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376544

RESUMO

Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic factors include cytokines and self-peptide-MHC, both of which are available from endogenous antigen-presenting cells (APC), we hypothesized that enhancing APC numbers in vivo can be a viable strategy to amplify the population of memory T cells. We evaluated this by acutely treating intact mice with FMS-like tyrosine kinase 3 ligand (Flt3l), which promotes expansion of APCs. Here we report that this treatment allowed for, an expansion of effector-memory CD4+ and CD8+ T cells as well as an increase in their expression of KLRG1 and CD25. In the lymph nodes and spleen, the expansion was limited to a specific CD8 (CD44-low but CD62L-) subset. Functionally, this subset is distinct from naïve T cells and could produce significant amounts of effector cytokines upon restimulation. Taken together, these data suggest that the administration of Flt3L can impact both APC turnover as well as a corresponding flux of specific subsets of CD8+ T cells in an intact peripheral immune compartment.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Camundongos , Animais , Baço/metabolismo , Contagem de Linfócitos , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Memória Imunológica
2.
Cell Rep ; 37(2): 109816, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644571

RESUMO

Cytokines are typically single gene products, except for the heterodimeric interleukin (IL)-12 family. The two subunits (IL-12p40 and IL-12p35) of the prototype IL-12 are known to be simultaneously co-expressed in activated myeloid cells, which secrete the fully active heterodimer to promote interferon (IFN)γ production in innate and adaptive cells. We find that chimeric mice containing mixtures of cells that can only express either IL-12p40 or IL-12p35, but not both together, generate functional IL-12. This alternate two-cell pathway requires IL-12p40 from hematopoietic cells to extracellularly associate with IL-12p35 from radiation-resistant cells. The two-cell mechanism is sufficient to propel local T cell differentiation in sites distal to the initial infection and helps control systemic dissemination of a pathogen, although not parasite burden, at the site of infection. Broadly, this suggests that early secretion of IL-12p40 monomers by sentinel cells at the infection site may help prepare distal host tissues for potential pathogen arrival.


Assuntos
Células Dendríticas/metabolismo , Subunidade p35 da Interleucina-12/metabolismo , Subunidade p40 da Interleucina-12/metabolismo , Leishmania major/patogenicidade , Leishmaniose Cutânea/metabolismo , Células Estromais/metabolismo , Linfócitos T/metabolismo , Animais , Comunicação Celular , Células Dendríticas/imunologia , Células Dendríticas/parasitologia , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita , Interferon gama/metabolismo , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Leishmania major/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Multimerização Proteica , Transdução de Sinais , Células Estromais/imunologia , Células Estromais/parasitologia , Linfócitos T/imunologia , Linfócitos T/parasitologia
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