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1.
Exp Hematol ; : 104256, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876254

RESUMEN

Acute myeloid leukemia (AML) is a genetically heterogeneous disease, in that a multitude of oncogenic drivers and chromosomal abnormalities have been identified and associated with the leukemic transformation of myeloid blasts. However, little is known as to how individual mutations influence the interaction between the immune system and AML cells and the efficacy of the immune system in AML disease control. In this review, we will discuss how AML cells potentially activate the immune system and what evidence there is to support the role of the immune system in controlling this disease. We will specifically examine the importance of antigen presentation in fostering an effective anti-AML immune response, explore the disruption of immune responses during AML disease progression, and discuss the emerging role of the oncoprotein MYC in driving immune suppression in AML.

2.
Nat Commun ; 15(1): 5497, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38944658

RESUMEN

Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4+ T cell subsets remain unresolved. Here, we examine antigen-experienced CD4+ T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic TEM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with TCM/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4+ T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4+ T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.


Asunto(s)
Linfocitos T CD4-Positivos , Malaria , Reinfección , Animales , Malaria/inmunología , Malaria/parasitología , Linfocitos T CD4-Positivos/inmunología , Ratones , Reinfección/inmunología , Células TH1/inmunología , Ratones Endogámicos C57BL , Bazo/inmunología , Bazo/parasitología , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética , Ratones Transgénicos , Femenino , Memoria Inmunológica
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