Редактирование: CCL4

C-C motif chemokine 4 precursor (G-26 T-lymphocyte-secreted protein) (HC21) (Lymphocyte activation gene 1 protein) (LAG-1) (MIP-1-beta(1-69)) (Macrophage inflammatory protein 1-beta) (MIP-1-beta) (PAT 744) (Protein H400) (SIS-gamma) (Small-inducible cytokine A4) (T-cell activation protein 2) (ACT-2) [Contains: MIP-1-beta(3-69)] [LAG1] [MIP1B] [SCYA4]

==Publications==

{{medline-entry
|title=Microglial translational profiling reveals a convergent [[APOE]] pathway from aging, amyloid, and tau.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30082275
|abstract=Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central [[APOE]]-driven network that converged on [[CCL3]] and [[CCL4]] across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this [[APOE]] network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid
* Amyloidosis
* Animals
* Apolipoproteins E
* Chemokine CCL3
* Chemokine CCL4
* Disease Models, Animal
* Female
* Male
* Mice
* Mice, Transgenic
* Microglia
* Signal Transduction
* tau Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122978
}}
{{medline-entry
|title=Time-Dependent Changes in Local and Serum Levels of Inflammatory Cytokines as Markers for Incised Wound Aging of Skeletal Muscles.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29760352
|abstract=Wound age estimation is an important research field in forensic pathology. The expression levels of cytokines in the incised skeletal muscle were analyzed using a mouse model to explore the applicability for wound aging. A 5-mm long incisional wound was made at the biceps femoris muscle, and the muscle and serum were sampled at 6, 12, 24 and 48 hours after injury. Using a multiplex bead-based immunoassay, we measured the tissue levels of nine cytokines (IL-1β, IL-6, IL-7, [[CCL2]], [[CCL3]], [[CCL4]], [[CXCL1]], [[CXCL2]], and [[CXCL1]]0), which are all involved in the pathways of inflammatory response and tissue injury. Immunoassay of post-injury muscle samples revealed significant increases in the levels of six cytokines, except for [[CCL3]], [[CCL4]] and IL-7, at 6 hours after injury. The elevated tissue levels of these six cytokines were maintained during 48 hours after injury, although the levels of IL-6 and [[CXCL1]] were significantly decreased at 12 hours. In case of [[CCL3]], its tissue levels were increased only at 12 hours. By contrast, [[CCL4]] and IL-7 levels were increased only at 48 hours. Moreover, serum levels of most cytokines, except for [[CXCL1]], remained unchanged during 24 hours after injury, followed by significant increases at 48 hours. Serum [[CXCL1]] levels were increased at 6 hours and then decreased to the basal levels. Thus, the significant increase in the muscle levels of [[CXCL1]] and IL-7 was observed at 6 and 48 hours after injury, respectively. Measuring muscle [[CXCL1]] and IL-7 levels is helpful for estimating incised wound aging.
|mesh-terms=* Aging
* Animals
* Biomarkers
* Cytokines
* Gene Expression Regulation
* Immunoassay
* Inflammation Mediators
* Male
* Mice, Inbred BALB C
* Muscle, Skeletal
* RNA, Messenger
* Time Factors
* Wounds and Injuries
|keywords=* bead-based immunoassay
* cytokines
* sharp force injury
* skeletal muscle
* wound aging
|full-text-url=https://sci-hub.do/10.1620/tjem.245.29
}}
{{medline-entry
|title=Human Body Composition and Immunity: Visceral Adipose Tissue Produces IL-15 and Muscle Strength Inversely Correlates with NK Cell Function in Elderly Humans.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29559978
|abstract=Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) are sources of IL-15 and IL-15 Rα, and (2) whether any of these tissues correlate with NK cell activity in elderly humans. We first investigated IL-15 and IL-15Rα RNA expression in paired muscle and SAT biopsies from healthy human subjects. Both tissues expressed these transcripts, but IL-15Rα RNA levels were higher in SAT than in skeletal muscle. We also investigated tissue obtained from surgeries and found that SAT and VAT expressed equivalent amounts of IL-15 and IL-15Rα RNA, respectively. Furthermore, stromal vascular fraction cells expressed more IL-15 RNA than did adipocytes. To test if these findings related to circulating IL-15 protein and NK cell function, we tested 50 healthy adults aged > 70 years old. Plasma IL-15 levels significantly correlated with abdominal VAT mass in the entire cohort and in non-obese subjects. However, plasma IL-15 levels did not correlate with skeletal muscle cross-sectional area and correlated inversely with muscle strength. Plasma IL-15 did correlate with NK cell cytotoxic granule exocytosis and with [[CCL4]] (MIP-1β) production in response to NKp46-crosslinking. Additionally, NK cell responses to K562 leukemia cells correlated inversely with muscle strength. With aging, immune function declines while infections, cancers, and deaths increase. We propose that VAT-derived IL-15 and IL-15Rα is a compensatory NK cell support mechanism in elderly humans.
|mesh-terms=* Adult
* Aged
* Aging
* Body Composition
* Cohort Studies
* Cytotoxicity, Immunologic
* Female
* Gene Expression Regulation
* Humans
* Immunity
* Interleukin-15
* Interleukin-15 Receptor alpha Subunit
* Intra-Abdominal Fat
* K562 Cells
* Killer Cells, Natural
* Male
* Middle Aged
* Muscle Strength
* Natural Cytotoxicity Triggering Receptor 1
* Young Adult
|keywords=* IL-15
* adipose tissue
* aging
* natural killer cell
* skeletal muscle strength
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845694
}}
{{medline-entry
|title=Age-related pro-inflammatory and pro-angiogenic changes in human aqueous humor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29487806
|abstract=To reveal age-related aqueous cytokine changes in human aqueous humor. Aqueous humor was collected from 12 young children (3-6.5 years old) and 71 healthy adults (22-106 years old) with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor (VEGF) were measured and analyzed. The following proteins showed significant increase from childhood to adult: interferon-gamma (IFN-γ), interleukin (IL)-13, IL-6, IL-12(p70), IL-10, [[CCL2]], [[CCL3]], [[CCL4]], [[CXCL8]], [[CXCL9]], [[CXCL10]], IFN-α2 and VEGF (all [i]P[/i]<0.05). IFN-γ, IL-13, IL-12(p70), IL-10, [[CCL3]], [[CXCL9]] and VEGF also showed moderate strength age-related increase in the adult group ([i]r[/i]>0.5). The strength of correlation between aging and [[CCL4]] were fair ([i]r[/i]=0.398). The concentrations of IL-2, IL-4, IL-5, IL-1β and [[TNF]]-α were low in both groups. From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.

|keywords=* aging
* aqueous humor
* cytokines
* macrophage
* parainflammation
* vascular endothelial growth factor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824071
}}
{{medline-entry
|title=Age-related decline of the acute local inflammation response: a mitigating role for the adenosine A  receptor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29064819
|abstract=Aging is accompanied by an increase in markers of innate immunity. How aging affects neutrophil functions remains of debate.The adenosine A  receptor (A R), essential to the resolution of inflammation, modulates neutrophil functions. We sought to determine whether or not A R protects against the effects of aging. We monitored neutrophil influx, viability, and activation as well as cytokine accumulation in wild-type (WT) and A R-knockout mice (KO) at three different ages.Several readouts decreased with aging: neutrophil counts in dorsal air pouches (by up to 55%), neutrophil viability (by up to 56%), elastase and total protein in exudates (by up to 80%), and local levels of cytokines (by up to 90%). Each of these parameters was significantly more affected in A R-KO mice. [[CXCL1]]-3 levels were largely unaffected. The effects of aging were not observed systemically. Preventing neutrophil influx into the air pouch caused a comparable cytokine pattern in young WT mice. Gene expression (mRNA) in leukocytes was affected, with [[CXCL1]] and [[CCL4]] increasing and with [[TNF]] and IL-1α decreasing. Aging has deleterious effects on the acute inflammatory response and neutrophil-related activities, and defective migration appears as an important factor. A functional A R signaling pathway delays some of these.
|mesh-terms=* Aging
* Animals
* Chemotaxis, Leukocyte
* Inflammation
* Mice
* Mice, Knockout
* Neutrophils
* Receptor, Adenosine A2A
|keywords=* adenosine
* aging
* apoptosis
* cytokines
* migration
* neutrophils
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680557
}}
{{medline-entry
|title=Simultaneous time course analysis of multiple markers based on DNA microarray in incised wound in skeletal muscle for wound aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27376479
|abstract=Assessment of incised wound age in skeletal muscles is important because fatal injuries are often complicated with muscle involvement. Transcriptome of injured skeletal muscle along with histopathological and immunohistochemistry staining, were analyzed to explore the biological effect of incised injuries using a mouse incised injury model. An incisional wound was made at the biceps femoris muscle of anesthetized mice, and the muscles were sampled at 6, 12, 24, 36 and 48h post-injury. DNA microarray analysis using RNA extracted from the muscle samples of 12h post-injury identified 3,655 upregulated and 3,583 downregulated genes. Referring to the results of the gene ontology and gene expression pathway analysis, time course expression of five cytokines, namely chemokine (C-C motif) ligand 4 ([[CCL4]]), chemokine (C-X-C motif) ligand 5 ([[CXCL5]]), interleukin-1 beta (IL-1β), interleukin- 6 (IL-6) and interleukin-7 (IL-7), were analyzed by quantative reverse transcription PCR (qRT-PCR). [[CXCL5]] was the most upregulated gene throughout the post-injury period with higher expression from 6 through 36h post injury. Upregulation of [[CCL4]] and IL-1β was also persisted until 36h post injury. IL-6 mRNA was highly and rapidly expressed at 6h post-injury followed by significant decrease at 12h. Unlike other four cytokines, IL-7 showed slow and steady increasing over time until 48h post-injury. Immunohistochemical staining of post-injury samples showed gradual mild increase of staining intensity proportional to increasing time points especially around the wound edges. The present study highlights the unique dynamics of each cytokine and reflects their roles in the process of muscle wound healing, and suggests the potential of them as a tool for forensic wound age estimation. 
|mesh-terms=* Animals
* Cytokines
* Forensic Pathology
* Gene Expression Regulation
* Interleukin-6
* Mice
* Muscle, Skeletal
* Oligonucleotide Array Sequence Analysis
* Time Factors
* Wound Healing
|keywords=* Cytokines
* DNA microarray
* Gene expression
* Incised wound
* Skeletal muscle
* Wound aging
|full-text-url=https://sci-hub.do/10.1016/j.forsciint.2016.06.027
}}
{{medline-entry
|title=Changes in the expression of the Toll-like receptor system in the aging rat kidneys.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24810370
|abstract=The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and [[HMGB1]], the TLRs ([[TLR1]]-[[TLR1]]1), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines [[CCL3]], [[CCL4]], [[CCL5]], [[CD80]], [[TNF]]-α, and IL-12b in the rat renal tissues of the various age groups. We found that during kidney aging, the HSP70 and [[HMGB1]] expression levels were significantly increased, and the expression levels of [[TLR1]], 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines [[CCL3]], [[CCL4]], [[CCL5]], [[CD80]], [[TNF]]-α, and IL-12b were significantly upregulated. These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors.
|mesh-terms=* Aging
* Animals
* Kidney
* Male
* NF-kappa B
* Phosphorylation
* Rats
* Rats, Inbred F344
* Signal Transduction
* Toll-Like Receptors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014502
}}
{{medline-entry
|title=Age-related brain expression and regulation of the chemokine [[CCL4]]/MIP-1β in APP/PS1 double-transgenic mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24607962
|abstract=The detrimental effect of activation of the chemokine [[CCL4]]/MIP-1β on neuronal integrity in patients with HIV-associated dementia has directed attention to the potential role of [[CCL4]] expression and regulation in Alzheimer disease. Here, we show that [[CCL4]] mRNA and protein are overexpressed in the brains of APPswe/PS1ΔE9 (APP/PS1) double-transgenic mice, a model of cerebral amyloid deposition; expression was minimal in brains from nontransgenic littermates or single-mutant controls. Increased levels of [[CCL4]] mRNA and protein directly correlated with the age-related progression of cerebral amyloid-β (Aβ) levels in APP/PS1 mice. We also found significantly increased expression of activating transcription factor 3 ([[ATF3]]), which was positively correlated with age-related Aβ deposition and [[CCL4]] in the brains of APP/PS1 mice. Results from chromatin immunoprecipitation-quantitative polymerase chain reaction confirmed that [[ATF3]] binds to the promoter region of the [[CCL4]] gene, consistent with a potential role in regulating [[CCL4]] transcription. Finally, elevated [[ATF3]] mRNA expression in APP/PS1 brains was associated with hypomethylation of the [[ATF3]] gene promoter region. These observations prompt the testable hypothesis for future study that [[CCL4]] overexpression, regulated in part by hypomethylation of the [[ATF3]] gene, may contribute to neuropathologic progression associated with amyloid deposition in Alzheimer disease. 
|mesh-terms=* Activating Transcription Factor 3
* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Brain
* Chemokine CCL4
* Chromatin Immunoprecipitation
* Disease Models, Animal
* Enzyme-Linked Immunosorbent Assay
* Gene Expression Regulation
* Glial Fibrillary Acidic Protein
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Mutation
* Presenilin-1

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977177
}}
{{medline-entry
|title=CD8 [[CD4]]5RA [[CCR7]] [[FOXP3]]  T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22821963
|abstract=CD8 T cells stimulated with a suboptimal dose of anti-CD3 Abs (100 pg/ml) in the presence of IL-15 retain a naive phenotype with expression of [[CD4]]5RA, [[CD28]], [[CD27]], and [[CCR7]] but acquire new functions and differentiate into immunosuppressive T cells. CD8 [[CCR7]]  regulatory T cells (Tregs) express [[FOXP3]] and prevent [[CD4]] T cells from responding to TCR stimulation and entering the cell cycle. Naive [[CD4]] T cells are more susceptible to inhibition than memory cells. The suppressive activity of CD8 [[CCR7]]  Tregs is not mediated by IL-10, TGF-β, CTLA-4, [[CCL4]], or adenosine and relies on interference with very early steps of the TCR signaling cascade. Specifically, CD8 [[CCR7]]  Tregs prevent TCR-induced phosphorylation of [[ZAP70]] and dampen the rise of intracellular calcium in [[CD4]] T cells. The inducibility of CD8 [[CCR7]]  Tregs is correlated with the age of the individual with PBLs of donors older than 60 y yielding low numbers of [[FOXP3]](low) CD8 Tregs. Loss of CD8 [[CCR7]]  Tregs in the elderly host may be of relevance in the aging immune system as immunosenescence is associated with a state of chronic smoldering inflammation.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* CD8 Antigens
* Cell Death
* Cell Differentiation
* Forkhead Transcription Factors
* Humans
* Immune Tolerance
* Leukocyte Common Antigens
* Middle Aged
* Primary Cell Culture
* Receptors, CCR7
* T-Lymphocyte Subsets
* T-Lymphocytes, Regulatory

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424334
}}
{{medline-entry
|title=Fat-storing multilocular cells expressing [[CCR5]] increase in the thymus with advancing age: potential role for [[CCR5]] ligands on the differentiation and migration of preadipocytes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20046229
|abstract=Age-associated thymic involution is characterized by decreased thymopoiesis, adipocyte deposition and changes in the expression of various thymic microenvironmental factors. In this work, we characterized the distribution of fat-storing cells within the aging thymus. We found an increase of unilocular adipocytes, ERTR7( ) and [[CCR5]](  )fat-storing multilocular cells in the thymic septa and parenchymal regions, thus suggesting that mesenchymal cells could be immigrating and differentiating in the aging thymus. We verified that the expression of [[CCR5]] and its ligands, [[CCL3]], [[CCL4]] and [[CCL5]], were increased in the thymus with age. Hypothesizing that the increased expression of chemokines and the [[CCR5]] receptor may play a role in adipocyte recruitment and/or differentiation within the aging thymus, we examined the potential role for [[CCR5]] signaling on adipocyte physiology using 3T3-L1 pre-adipocyte cell line. Increased expression of the adipocyte differentiation markers, PPARgamma2 and aP2 in 3T3-L1 cells was observed under treatment with [[CCR5]] ligands. Moreover, 3T3-L1 cells demonstrated an ability to migrate in vitro in response to [[CCR5]] ligands. We believe that the increased presence of fat-storing cells expressing [[CCR5]] within the aging thymus strongly suggests that these cells may be an active component of the thymic stromal cell compartment in the physiology of thymic aging. Moreover, we found that adipocyte differentiation appear to be influenced by the proinflammatory chemokines, [[CCL3]], [[CCL4]] and [[CCL5]].
|mesh-terms=* 3T3-L1 Cells
* Adipocytes
* Aging
* Animals
* Blotting, Western
* Cell Differentiation
* Cell Movement
* Chemokine CCL3
* Chemokine CCL4
* Chemokine CCL5
* Immunohistochemistry
* Mice
* Mice, Inbred BALB C
* Oligonucleotide Array Sequence Analysis
* Receptors, CCR5
* Reverse Transcriptase Polymerase Chain Reaction
* Thymus Gland
|keywords=* adipocyte
* adipokines
* aging
* chemokines
* chemotaxis
* differentiation
* involution
* thymus
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792732
}}
{{medline-entry
|title=[[CCL4]] protects from type 1 diabetes by altering islet beta-cell-targeted inflammatory responses.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17327452
|abstract=We previously reported that interleukin (IL)-4 treatment of nonobese diabetic (NOD) mice elevates intrapancreatic [[CCL4]] expression and protects from type 1 diabetes. Here, we show that antibody neutralization of [[CCL4]] abrogates the ability of T-cells from IL-4-treated NOD mice to transfer protection against type 1 diabetes. Intradermal delivery of [[CCL4]] via a plasmid vector stabilized by incorporation of the Epstein-Barr virus EBNA1/oriP episomal maintenance replicon (pHERO8100-[[CCL4]]) to NOD mice beginning at later stages of disease progression protects against type 1 diabetes. This protection was associated with a Th2-like response in the spleen and pancreas; decreased recruitment of activated CD8( ) T-cells to islets, accompanied by diminished [[CCR5]] expression on CD8( ) T-cells; and regulatory T-cell activity in the draining pancreatic lymph nodes. Thus, inflammatory responses that target islet beta-cells are suppressed by [[CCL4]], which implicates the use of [[CCL4]] therapeutically to prevent type 1 diabetes.
|mesh-terms=* Aging
* Animals
* Chemokine CCL4
* Chemokines, CC
* Diabetes Mellitus, Type 1
* Genetic Therapy
* Inflammation
* Insulin-Secreting Cells
* Interleukin-4
* Islets of Langerhans Transplantation
* Mice
* Mice, Inbred NOD
* Mice, SCID
* Mice, Transgenic
* Spleen
* T-Lymphocytes

|full-text-url=https://sci-hub.do/10.2337/db06-0619
}}
{{medline-entry
|title=Generation and growth of [[CD28]]nullCD8  memory T cells mediated by IL-15 and its induced cytokines.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17114451
|abstract=Accumulation of [[CD28]](null)CD8  T cells and the defects of these cells in response to antigenic stimulation are the hallmarks of age-associated decline of T cell function. However, the mechanism of these age-associated changes is not fully understood. In this study, we report an analysis of the growth of human [[CD28]](null) and [[CD28]] CD8  memory T cells in response to homeostatic cytokine IL-15 in vitro. We showed that 1) there was no proliferative defect of [[CD28]](null)CD8  memory T cells in response to IL-15 compared with their [[CD28]]  counterparts; 2) stable loss of [[CD28]] expression occurred in those actively dividing [[CD28]] CD8  memory T cells responding to IL-15; 3) the loss of [[CD28]] was in part mediated by [[TNF]]-alpha that was induced by IL-15; and 4) [[CCL4]] (MIP-1beta), also induced by IL-15, had a significant inhibitory effect on the growth of [[CD28]](null) cells, which in turn down-regulated their expression of [[CCL4]] receptor [[CCR5]]. Together, these findings demonstrate that [[CD28]](null)CD8  memory T cells proliferate normally in response to IL-15 and that IL-15 and its induced cytokines regulate the generation and growth of [[CD28]](null)CD8  T cells, suggesting a possible role of IL-15 in the increase in [[CD28]](null)CD8  T cells that occurs with aging.
|mesh-terms=* Aging
* CD28 Antigens
* CD8-Positive T-Lymphocytes
* Cell Proliferation
* Cytokines
* Humans
* Immunologic Memory
* Interleukin-15
* Reverse Transcriptase Polymerase Chain Reaction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262925
}}