Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological nonresponders.
Eur J Immunol
; 51(8): 2027-2039, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33974710
ABSTRACT
Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8+ T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções por HIV
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Interleucina-7
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Linfócitos T CD8-Positivos
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Memória Imunológica
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China