Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood

Yu, Jing; Gravenstein, Stefan; Chaganty, N. Rao; Chen, Nianyong; Lyerly, H. Kim; Joyce, Sebastian; Deng, Yuping

doi:10.1016/j.exger.2007.01.009

Cited by 88 publications

(72 citation statements)

References 61 publications

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“…10,37 Despite there being no significant difference in NKT cell frequency between patients with MDS and healthy donors, we separately compared age-matched control donors to patients with MDS to take into account reports that the frequency and subset distribution of NKT cells can vary between age groups. [38][39][40][41] This was not taken into account by earlier studies of patients with MDS; 10-12 however, we found no evidence of a difference in NKT cell frequency between patients with MDS (age range 45-89 years; median 61 years) and age-matched control subjects (age range 45-71 years; median 59 years) (Figure 1c).…”

Section: Nkt Cell Compartments Of Patients With Mds Before Therapycontrasting

confidence: 47%

“…This was potentially important because the frequency of NKT cells declines naturally with age and MDS usually develops in patients aged over 50 years. [38][39][40][41] Somewhat surprisingly, patients with MDS had similar NKT cell frequency (and NKT cell subset distribution) to a healthy age-matched control group, as well as to a larger control group that was not age-matched (as per previous studies). We note in retrospect, however, that the reports of age-related decline in NKT cell frequency were based on a significantly older group of donors than the patients with MDS in this study (B80 þ years compared to B61 years), 38,41 or reported only a weak correlation between age and NKT cell frequency that was not evident among patient subgroups with cancer.…”

Section: Discussionmentioning

confidence: 80%

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Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

et al. 2010

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Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.

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Section: Nkt Cell Compartments Of Patients With Mds Before Therapycontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 80%

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

et al. 2010

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“…5). A reduction was also observed in the ASA patients as compared with the young healthy individuals (po0.01), possibly reflecting an age-related effect on this lymphocyte subset [25]. These findings raise interesting issues regarding the fate of iNKT cells in peripheral blood of SA atherosclerotic patients: are they reduced because of lack of proliferative responsiveness to stimulatory lipids, increased apoptosis or increased extravasation into tissues?…”

Section: Cd1dmentioning

confidence: 84%

Invariant natural killer T cells: Linking inflammation and neovascularization in human atherosclerosis

et al. 2010

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Atherosclerosis, a chronic inflammatory lipid storage disease of large arteries, is complicated by cardiovascular events usually precipitated by plaque rupture or erosion. Inflammation participates in lesion progression and plaque rupture. Identification of leukocyte populations involved in plaque destabilization is important for effective prevention of cardiovascular events. This study investigates CD1d-expressing cells and invariant NKT cells (iNKT) in human arterial tissue, their correlation with disease severity and symptoms, and potential mechanisms for their involvement in plaque formation and/ or destabilization. CD1d-expressing cells were present in advanced plaques in patients who suffered from cardiovascular events in the past and were most abundant in plaques with ectopic neovascularization. Confocal microscopy detected iNKT cells in plaques, and plaque-derived iNKT cell lines promptly produced proinflammatory cytokines when stimulated by CD1d-expressing APC-presenting a-galactosylceramide lipid antigen. Furthermore, iNKT cells were diminished in the circulating blood of patients with symptomatic atherosclerosis. Activated iNKT cell-derived culture supernatants showed angiogenic activity in a human microvascular endothelial cell line HMEC-1-spheroid model of in vitro angiogenesis and strongly activated human microvascular endothelial cell line HMEC-1 migration. This functional activity was ascribed to IL-8 released by iNKT cells upon lipid recognition. These findings introduce iNKT cells as novel cellular candidates promoting plaque neovascularization and destabilization in human atherosclerosis.

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“…One of the most recognized effects of aging is the decline in immune function, or more precisely the age-associated immune deregulation, 50 that includes a decrease in the proliferative response to mitogens, low activity of natural killer (NK) cells, 51,52 a progressive involution of the thymus together with lower number and reduced response of immune T cells, 53 and increased levels of pro-inflammatory cytokines. 24,33,34 This imbalance, commonly called "immunosenescence", may contribute to explain the high susceptibility of elderly people to disease.…”

Section: Physiological and Immune Status In The Elderlymentioning

confidence: 99%

Nutrition and the gut microbiome in the elderly

et al. 2016

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The gut microbiota is the assembly of microorganisms living in our intestine and their genomes are known as the microbiome. The correct composition and functionality of this microbiome is essential for maintaining a "healthy status." Aging is related to changes in the gut microbiota which are frequently associated with physiological modifications of the gastrointestinal tract, as well as, to changes in dietary patterns, together with a concomitant decline in cognitive and immune function, all together contributing to frailty. Therefore, nutritional strategies directed at restoring the microbiota in the elderly have to be addressed from a global perspective, considering not only the microbiota but also other extra-intestinal targets of action. The present review aims at summarizing the current knowledge on intestinal microbiota alterations and other functions impaired in the elderly and to analyze tools for implementing nutritional strategies, through the use of probiotics, prebiotics or specific nutrients in order to counterbalance such alterations.

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Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood

Cited by 88 publications

References 61 publications

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

Invariant natural killer T cells: Linking inflammation and neovascularization in human atherosclerosis

Nutrition and the gut microbiome in the elderly

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