Discovery of CD3+CD19+ cells, a novel lymphocyte subset with a potential role in human immunodeficiency virus‐Mycobacterium tuberculosis coinfection, using mass cytometry

Li, Qian; Wang, Jun; Zhang, Min; Tang, Yang; Lu, Hongzhou

doi:10.1002/ctm2.681

Cited by 10 publications

(9 citation statements)

References 9 publications

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“…Different from the abovementioned studies, recent studies reported a previously unknown lymphocyte subset that co-expressed CD3 and CD19 in human 21,22 . This subset of lymphocytes might play crucial roles in type I diabetes 21 and infectious diseases 22 . However, its presence and function in normal physiological conditions have not been fully demonstrated.…”

Section: Introductionmentioning

confidence: 77%

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities

Wan

Zhang²,

Guo³

et al. 2023

Preprint

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T cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. These CD3+CD19+ lymphocytes show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood. Functional assays show that these biphenotypic lymphocytes can be activated through stimulating TCR or BCR signaling pathways. Moreover, we show that these cells actively participate both the humoral and cellular immune responses elicited by vaccination. Compared to conventional T cells, these biphenotypic lymphocytes can secrete a higher level of IL-2 but a lower level of TNF-α upon antigen specific stimulation. An equivalent lymphocyte subset is found in freshly isolated human PBMCs and exhibits similar functionality, albeit at a lower frequency than in mice.

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Section: Introductionmentioning

confidence: 77%

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities

Wan

Zhang²,

Guo³

et al. 2023

Preprint

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“…Cluster 8 expressed genes such as MZB1 encoding marginal zone B and B1 cell-specific protein along with other genes such as APOE, S100A6, AHNAK, and PAFAH1B3, which are involved in the activation of T lymphocytes by antigen presentation, termed as marginal zone B cells. Cluster 9 expressed genes such as CD3E, CD3D, CD3G, IL7R, TRBC2, TRAC, and TCF7 that are related to T-cell proliferation and T-cell receptors, termed as CD3+ B cells ( 77 ). Finally, in cluster 10, there were two subsets of cells—in one subcluster, there was increased expression of antibody-related genes such as IGKC, IGHM, IGLC1, IGLV1, JCHAIN, FAM214A, and XBP1, reflecting antibody-secreting cells (ASCs) ( 78 ).…”

Section: Resultsmentioning

confidence: 99%

“…Cluster 5 expressed CD19, which is similar to the cluster 9 in the CD3+ B-cell population. CD3 + CD19 + lymphocytes subsets have been identified in disease conditions such as HIV/ Mycobacterium co-infections ( 77 ). Cluster 7 expressed CD8a and CD8b1 representing the cytotoxic CD8 subset of T cells ( Figure 10C ).…”

Section: Resultsmentioning

confidence: 99%

“…Qing et al. reported that CD3+CD19+ cell counts were observed to be markedly reduced in patients with HIV/ Mycobacterium co-infection compared to healthy controls ( 77 ). They observed that the inhibitory molecules PD1 and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) were highly expressed in the CD3+CD19+ cells in the HIV/ Mycobacterium co-infection group, indicating a phenotype involving greater suppression of the adaptive immune response.…”

Section: Discussionmentioning

confidence: 99%

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Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi

Kumaresan,

Ingle,

Kilgore

et al. 2023

Front. Immunol.

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IntroductionLyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen Borrelia burgdorferi (Bb). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with Bb reflecting a subset of inflammatory responses observed in human Lyme disease. The advent of post-genomic methodologies and genomic data sets enables dissecting the host responses to advance therapeutic options for limiting the pathogen transmission and/or treatment of Lyme disease.MethodsIn this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing Bb to sort GFP+ splenocytes and GFP− bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against Bb.ResultsThese data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H/HeN mice in response to Bb infection. Increased mRNA abundance of apoptosis-related genes was observed in neutrophils and macrophages clustered from GFP+ splenocytes. Moreover, complement-mediated phagocytosis-related genes such as C1q and Ficolin were elevated in an inflammatory macrophage subset, suggesting upregulation of these genes during the interaction of macrophages with Bb-infected neutrophils. In addition, the role of DUSP1 in regulating the expression of Casp3 and pro-inflammatory cytokines Cxcl1, Cxcl2, Il1b, and Ccl5 in Bb-infected neutrophils were identified.DiscussionThese findings serve as a growing catalog of cell phenotypes/biomarkers among murine splenocytes that can be exploited for limiting spirochetal burden to limit the transmission of the agent of Lyme disease to humans via reservoir hosts.

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“…Although increased to a certain degree in Type 2 and Type 3 groups, interestingly, CD3+CD19+ cells characterized by high CD45, CD3, and CD19 expression levels were mainly found in vaccinated individuals in the Type 1 and HDV groups relative to the HD group. The CD3+CD19+ cells were present in peripheral blood samples from patients with HIV/mycobacterium tuberculosis infection and patients with cancer, reflecting the adaptive immune landscape ( 35 , 36 ). Combining findings from our study and other studies, although all the studies showed that CD3+CD19+ cells were present commonly in the peripheral blood of healthy donors, the percentage of CD3+CD19+ cells in patients with cancer/vaccination population was significantly higher than that of CD3+CD19+ cells in healthy donors.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines

et al. 2022

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SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

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Discovery of CD3⁺CD19⁺ cells, a novel lymphocyte subset with a potential role in human immunodeficiency virus‐Mycobacterium tuberculosis coinfection, using mass cytometry

Cited by 10 publications

References 9 publications

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities

Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines

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