The Function of CD3+CD56+NKT-Like Cells in HIV-Infected Individuals

Jiang, Yongjun; Cui, Xiaohui; Zhang, Jian; Zhou, Fangyuan; Zhang, Zining; Fu, Yajing; Xu, Junjie; Chu, Zhenxing; Liu, Jing; Han, Xiaoxu; Liao, Christina; Wang, Yanan; Cao, Yaming

doi:10.1155/2014/863625

Cited by 39 publications

(28 citation statements)

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“…NKT-like cells share several characteristics with NK cells [ 31 ] and serve as frontline innate immune effectors and potential regulators of adaptive immune responses against microorganisms [ 32 ]. Although only a trend, the increase of NKT-like cells observed during treatment could be explained by their ability to serve as an early source of regulatory cytokines and their degranulation-related killing function.…”

Section: Discussionmentioning

confidence: 99%

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

et al. 2015

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BackgroundThe effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG) treatment versus local heat therapy (Thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities.MethodsWe studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparameter flow cytometry, lymphoproliferative assays and cytokine production were analyzed in order to investigate the differences in the immune responses of subjects before, on and after treatment.ResultsHealing cutaneous leishmaniasis lead to a significant decline in circulating T cells and NKT-like cells, accompanied by an expansion in NK cells, regardless of treatment modality. Functional changes involved decreased antigen specific CD4+ T cell proliferation (hyporesponsiveness) seen with CD8+ T cell depletion. Moreover, the healing (or healed) state was characterized by fewer circulating regulatory T cells, reduced IFN-γ production and an overall contraction in polyfunctional CD4+ T cells.ConclusionHealing from cutaneous Leishmaniasis is a dynamic process that alters circulating lymphocyte populations and subsets of T, NK and NKT-like cells. Immunology of healing, through local or systemic treatments, culminated in similar changes in frequency, quality, and antigen specific responsiveness with immunomodulation possibly via a CD8+ T cell dependent mechanism. Understanding the evolving immunologic changes during healing of human leishmaniasis informs protective immune mechanisms.

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Section: Discussionmentioning

confidence: 99%

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

et al. 2015

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“…NKT-like cells constitute approximately 5-15% of the peripheral T-cell population and up to 50% of T lymphocytes in the human liver, although the liver population is on average around 30% [9]. They can mediate MHC-restricted and MHC-unrestricted cytotoxicity and secrete many cytokines, including IFN-g, which induces antiviral reaction and modulates Th1 immune responses [8,10].…”

Section: Introductionmentioning

confidence: 99%

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

Kaszubowska

Foerster

Kwiatkowski

et al. 2019

Folia Histochem Cytobiol.

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Introduction. NKT-like cells are "non-classical", "CD1d-independent" NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing. Material and methods. The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess NKT-like (CD3+CD56+) and T (CD3+) cell populations. Results. The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable. Conclusions. The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

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“…The function of these cells in context of malaria remains unexplored, but studies in other disease models have established these cells as cytolytic and capable of secreting Th1 inflammatory cytokines [56]. For example, these NKT cells are critical effectors in the maintenance of long-term non-progressor status in HIV-infected individuals [57]. Interestingly, NKT-like cells have also recently been reported to suppress over-activated immune processes through killing of antigen bearing dendritic cells [58].…”

Section: Discussionmentioning

confidence: 99%

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

Lehmann

Campo

Cicéron³

et al. 2017

PLoS ONE

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Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-), and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+) and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56-) T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that delineate individuals into asymptomatic and symptomatic phenotypes. Future investigations using large scale biological data sets analyzing multiple components of adaptive immunity, could collectively define which cellular responses and molecular correlates of disease outcome are malaria region specific, and which are truly generalizable features of asymptomatic Plasmodium immunity, a research goal of critical priority.

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The Function of CD3⁺CD56⁺NKT-Like Cells in HIV-Infected Individuals

Cited by 39 publications

References 30 publications

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

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