RESUMO
BACKGROUND: The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. METHODS: By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital's clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. RESULTS: The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients' tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). CONCLUSIONS: In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development.
Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Prognóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Citocinas/metabolismo , Albuminas/uso terapêutico , Microambiente Tumoral , Metiltransferases/metabolismo , Proteínas Repressoras/metabolismoRESUMO
Senescent T cells have been described during aging, chronic infections, and cancer; however, a comprehensive study of the phenotype, function, and transcriptional program of this T cell population in breast cancer (BC) patients is missing. Compared to healthy donors (HDs), BC patients exhibit an accumulation of KLRG-1+CD57+ CD4+ and CD8+ T cells in peripheral blood. These T cells infiltrate tumors and tumor-draining lymph nodes. KLRG-1+CD57+ CD4+ and CD8+ T cells from BC patients and HDs exhibit features of senescence, and despite their inhibitory receptor expression, they produce more effector cytokines and exhibit higher expression of Perforin, Granzyme B, and CD107a than non-senescent subsets. When compared to blood counterparts, tumor-infiltrating senescent CD4+ T cells show similar surface phenotype but reduced cytokine production. Transcriptional profiling of senescent CD4+ T cells from the peripheral blood of BC patients reveals enrichment in genes associated with NK or CD8+-mediated cytotoxicity, TCR-mediated stimulation, and cell exhaustion compared to non-senescent T cells. Comparison of the transcriptional profile of senescent CD4+ T cells from peripheral blood of BC patients with those of HDs highlighted marked similarities but also relevant differences. Senescent CD4+ T cells from BC patients show enrichment in T-cell signaling, processes involved in DNA replication, p53 pathways, oncogene-induced senescence, among others compared to their counterparts in HDs. High gene expression of CD4, KLRG-1, and B3GAT1 (CD57), which correlates with increased overall survival for BC patients, underscores the usefulness of the evaluation of the frequency of senescent CD4+ T cells as a biomarker in the follow-up of patients.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Senescência Celular , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias da Mama/etiologia , Antígenos CD57/metabolismo , Estudos de Casos e Controles , Senescência Celular/genética , Senescência Celular/imunologia , Citotoxicidade Imunológica , Feminino , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Lectinas Tipo C/metabolismo , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Receptores Imunológicos/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologiaRESUMO
Asthma is a chronic immunological disease affecting all age groups, but often starting in childhood. Although it has long been ascribed to a single pathology, recent studies have highlighted its heterogeneity due to the potential involvement of various pathogenic mechanisms. Here, we present our current understanding of the role of innate-like T (ILT) cells in asthma pathogenesis. These cells constitute a specific family mainly comprising γδT, invariant natural killer (iNKT) and mucosal-associated invariant (MAIT) T cells. They all share the ability to massively secrete a wide range of cytokines in a T-cell receptor (TCR)-dependent or -independent manner. ILT cells are prevalent in mucosal tissues, including airways, where their innate and adaptive immune functions consist primarily in protecting tissue integrity. However, ILT cells may also have detrimental effects leading to asthma symptoms. The immune mechanisms through which this pathogenic effect occurs will be discussed in this overview.
Assuntos
Asma/etiologia , Asma/metabolismo , Suscetibilidade a Doenças , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Asma/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/patologiaRESUMO
Dengue virus (DENV) co-circulation in Brazil represents a challenge for treatment and vaccine development. Despite public health impact, the occurrence of coinfections with other viruses is a common event. Increased T cell activation and altered inflammatory response are found during DENV coinfection with Human Immunodeficiency Virus (HIV) impacting HIV-pathogenesis. Even with Antiretroviral therapy (ART), HIV- treated patients had chronic immune activation and lymphocyte apoptosis. However, apoptotic mechanisms have not been investigated during coinfection with DENV. Our attention was attracted to apoptotic cell markers expressions in PBMCs from DENV and DENV/HIV coinfected patients. We found CD4/CD8 ratio inversion in most coinfected patients. CD4 T and CD8 T-cell subsets from DENV and DENV/HIV groups expressed low levels of anti-apoptotic protein Bcl-2. Furthermore, CD8 CD95 double positive cells frequency expressing low levels of Bcl-2 were significantly higher in these patients. Additionally, the density of Bcl-2 on classical monocytes (CD14++CD16-) was significantly lower during DENV infection. Upregulation of pro-apoptotic proteins and anti-apoptotic proteins were found in DENV and DENV/HIV, while catalase, an antioxidant protein, was upregulated mainly in DENV/HIV coinfection. These findings provide evidence of apoptosis triggering during DENV/HIV coinfection, which may contribute to knowledge of immunological response during DENV acute infection in HIV-patients treated with ART.
Assuntos
Apoptose/genética , Dengue/sangue , Infecções por HIV/sangue , Subpopulações de Linfócitos T/imunologia , Doença Aguda/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Coinfecção/sangue , Coinfecção/imunologia , Coinfecção/virologia , Dengue/imunologia , Dengue/patologia , Dengue/virologia , Vírus da Dengue/patogenicidade , Feminino , HIV/patogenicidade , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Leucócitos Mononucleares/virologia , Ativação Linfocitária/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Subpopulações de Linfócitos T/patologia , Adulto JovemRESUMO
The rationale for a type 17 signature in the pathogenesis of spondyloarthritis (SpA) has been increasing and being ratified in studies recently. IL-7 is a cytokine whose ability to stimulate IL-17 production in both innate and adaptive immunity cells has made it a promising target not only for a better understanding of the disease as well as an important potential therapeutic target in patients with SpA.
Assuntos
Citocinas/metabolismo , Suscetibilidade a Doenças , Interleucina-7/metabolismo , Espondilartrite/etiologia , Espondilartrite/metabolismo , Imunidade Adaptativa , Animais , Citocinas/genética , Fibrose , Humanos , Imunidade Inata , Interleucina-7/genética , Ligação Proteica , Receptores de Citocinas/metabolismo , Transdução de Sinais , Espondilartrite/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologiaRESUMO
BACKGROUND: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. OBJECTIVE: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. METHODS: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. RESULTS: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. CONCLUSION: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.
Assuntos
Pitiríase Rósea/patologia , Subpopulações de Linfócitos T/patologia , Adolescente , Adulto , Biópsia , Complexo CD3/análise , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Imunidade Celular , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Masculino , Pessoa de Meia-Idade , Pitiríase Rósea/imunologia , Valores de Referência , Coloração e Rotulagem , Subpopulações de Linfócitos T/imunologia , Fatores de Tempo , Adulto JovemRESUMO
Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Subpopulações de Linfócitos T/patologia , Pitiríase Rósea/patologia , Valores de Referência , Coloração e Rotulagem , Fatores de Tempo , Biópsia , Imuno-Histoquímica , Linfócitos T CD4-Positivos/patologia , Subpopulações de Linfócitos T/imunologia , Pitiríase Rósea/imunologia , Antígenos Comuns de Leucócito/análise , Complexo CD3/análise , Linfócitos T CD8-Positivos/patologia , Imunidade CelularRESUMO
The objective of this study was to evaluate the frequency of CD4+ T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (Treg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4+ T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4+ T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3+ and T-box 21 ( Tbet+) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = -0·531; P = 0·028) and with Tbet in renal interstitium (Rho = -0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4+ T cells were not different between LN and DC.
Assuntos
Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Fator de Transcrição GATA3/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Nefrite Lúpica/patologia , Nefrite Lúpica/terapia , Contagem de Linfócitos , Masculino , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.
Assuntos
Imunoglobulina G/sangue , Infecções/sangue , Infecções/patologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Subpopulações de Linfócitos T/patologia , Adolescente , Adulto , Idoso , Anticorpos Antinucleares/sangue , Complemento C3/análise , Complemento C4/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Infecções/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Reação em Cadeia da Polimerase , Fatores de Risco , Soroglobulinas/análise , Estatísticas não Paramétricas , Subpopulações de Linfócitos T/imunologia , Adulto JovemRESUMO
Studies indicate that exercise might delay human biological aging, but the effects of long-term exercise on T cell function are not well known. We tested the hypothesis that moderate or intense exercise lifestyle may attenuate the effects of aging on the telomere length and the survival and composition of T cell subpopulations. Elderly (65-85 years) with intense training lifestyle (IT, n = 15), moderate training lifestyle (MT, n = 16), and who never trained (NT, n = 15) were studied. Although the three groups presented the age-associated contraction of the TCD4(+)/TCD8(+) naïve compartments and expansion of the memory compartments, both training modalities were associated with lower proportion of terminally differentiated (CD45RA(+)CCR7(neg)) TCD4(+) and TCD8(+) cells, although among the latter cells, the reduction reached statistical significance only with IT. MT was associated with higher proportion of central memory TCD4(+) cells, while IT was associated with higher proportion of effector memory TCD8(+) cells. However, both training lifestyles were unable to modify the proportion of senescent (CD28(neg)) TCD8(+) cells. Telomeres were longer in T cells in both training groups; with IT, telomere length increased mainly in TCD8(+) cells, whereas with MT, a modest increase in telomere length was observed in both TCD8(+) and TCD4(+) cells. Reduced commitment to apoptosis of resting T cells, as assessed by caspase-3 and Bcl-2 expression, was seen predominantly with IT. Measurement of pro-inflammatory cytokines in serum and peripheral blood mononuclear cell (PBMC)'s supernatants did not show chronic low-grade inflammation in any of the groups. In conclusion, MT and IT lifestyles attenuated some of the effects of aging on the immune system.