ABSTRACT
Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Subject(s)
Animals , Humans , Mice , CD4-Positive T-Lymphocytes/pathology , Cell Differentiation , Encephalomyelitis, Autoimmune, Experimental/metabolism , Mice, Inbred C57BL , Multiple Sclerosis , Th1 Cells/pathologyABSTRACT
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.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , T-Lymphocyte Subsets/pathology , Pityriasis Rosea/pathology , Reference Values , Staining and Labeling , Time Factors , Biopsy , Immunohistochemistry , CD4-Positive T-Lymphocytes/pathology , T-Lymphocyte Subsets/immunology , Pityriasis Rosea/immunology , Leukocyte Common Antigens/analysis , CD3 Complex/analysis , CD8-Positive T-Lymphocytes/pathology , Immunity, CellularABSTRACT
Abstract: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a rare disease, with an indolent evolution and benign course. The classic presentation is a solitary nodule on the face or trunk. The disorder's rarity and clinical and histopathological characteristics, can make the diagnosis difficult. We present the case of a 36-year-old Caucasian woman with a purplish erythematous nodule, hardened, shiny, asymptomatic, on the left nasal ala, which had grown progressively for 45 days. Histopathological examination and immunohistochemistry panel demonstrated alterations consistent with primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. There was complete remission of the condition within 60 days of treatment with potent occlusive corticosteroids.
Subject(s)
Humans , Female , Adult , CD4-Positive T-Lymphocytes/pathology , Erythema/pathology , Lymphoproliferative Disorders/pathology , Skin Neoplasms/pathology , Immunohistochemistry , Lymphoma, T-Cell, Cutaneous/pathologyABSTRACT
Abstract Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.
Subject(s)
Humans , Periapical Abscess/metabolism , Periapical Granuloma/metabolism , Periapical Granuloma/pathology , Interleukin-17/analysis , Periapical Abscess/pathology , Reference Values , Biopsy , Immunohistochemistry , Pancreatic Elastase/analysis , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/chemistry , CD4 Antigens/analysis , Fluorescent Antibody Technique , CD8 Antigens/analysis , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/chemistry , Neutrophil InfiltrationABSTRACT
PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways and progressive destruction of lung parenchyma. Apoptosis is critical for the maintenance of normal tissue homeostasis and is in equilibrium with proliferation and differentiation. This study was undertaken to investigate relationship between apoptosis of peripheral blood lymphocytes during exacerbation of COPD and inflammatory response that characterizes this condition. MATERIALS AND METHODS: Seventeen patients with COPD exacerbation, 21 stable COPD, and 12 control subjects were included. T lymphocytes were isolated from peripheral blood using MACS. Apoptosis of T lymphocytes was assessed with FACS using annexin V and 7-aminoactinomycin. Serum levels of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha were determined by an immunoassay technique. RESULTS: There was significantly increased percentage of apoptotic lymphocytes, CD 4+, and CD 8+ T cells in the peripheral blood of patients with exacerbation of COPD compared with stable COPD. Serum levels of IL-6, IL-8, and TNF-alpha were significantly increased in patients with exacerbation of COPD compared with stable COPD. Only TNF-alpha presented a positive correlation with apoptotic lymphocytes in patients with exacerbation of COPD. CONCLUSION: Increased apoptotic lymphocytes may be associated with upregulation of TNF-alpha in the peripheral blood of patients with acute exacerbation of COPD.
Subject(s)
Humans , Apoptosis , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Flow Cytometry , Interleukin-6/blood , Interleukin-8/blood , Pulmonary Disease, Chronic Obstructive/blood , T-Lymphocytes/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
Cryptococcus neoformans commonly causes opportunistic infections in immunocompromised patients, especially in patients with AIDS. CD4+ T-lymphocytopenia in AIDS indicates an increased risk of opportunistic infection and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL) is characterized by depletions in the CD4+ T-cell subsets, without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, and T-cell subsets should be evaluated in patients who present with unusual opportunistic infections. We report a case of pulmonary cryptococcosis and lung cancer in a patient with persistently low CD4+ cell counts, without evidence of HIV infection.
Subject(s)
Aged , Humans , Male , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/pathology , Carcinoma, Non-Small-Cell Lung/complications , Cryptococcosis/complications , Lung Neoplasms/complications , Lymphopenia/complicationsABSTRACT
A 65 years old male, retired chemical factory worker presented with generalized erythematous plaques of various sizes for 2 years. Sun exposure of the skin lesion was painful and pruritic. Lymph nodes were palpable in the neck, axilla and inguinal region after the appearance of skin lesions. He did not give any history of prolonged pyrexic illness, night sweating and significant weight loss. On peripheral flood film examination, lymphocytosis and eosinophilia with few atypical lymphocytes suggestive of Sezary cells were noted. Histopathological examination of skin tissue confirmed the diagnosis of mycosis fungoides.
Subject(s)
Aged , CD4-Positive T-Lymphocytes/pathology , Humans , Male , Mycosis Fungoides/diagnosisABSTRACT
The present article discusses CD4+ T -cell interaction and cytokine production after HIV-1 infection and progression to AIDS. On the basis of the experience of the author with biological fluids obtained from patients suspected of having AIDS and the recently available data concerning this matter, a model is proposed for the CD4+ T -cells network and CD4+ T -cells destruction during this infection. The mechanism of cellular killing involves apoptosis and preferential destruction of activated TH0/TH2-type cells. This type of cells is generated as an immune response to HIV-1 itself or to allergens and helminth infestations. The virus replicates more effectively in activated TH0/TH2-type cells and this contributes to the development of full-blown AIDS. The author has previously proposed the hypothesis of an elevation in IL-5 production during later stages of the diseazse and the use of eosinophilia of unknown etiology as a prognostic marker of AIDS in developing countries (Caterino-de-Araujo (1994). Immunology Today, 15: 498-499). At the present time, this proposition is confirmed and the use of eosinophilia as an indicator of a shift to a TH0/TH2-type response that predicts progression to AIDS is justified
Subject(s)
Humans , Apoptosis/physiology , CD4-Positive T-Lymphocytes/pathology , /physiology , Cytokines/biosynthesis , Acquired Immunodeficiency Syndrome/pathology , Eosinophilia/diagnosis , Interleukin-5/biosynthesisSubject(s)
HIV Infections/pathology , HIV Infections/physiopathology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , HIV Infections/epidemiology , HIV Infections/immunology , HIV/immunology , HIV/isolation & purification , HIV/pathogenicity , HIV/physiology , Macrophages/pathology , Monocytes/pathologySubject(s)
Male , Female , Humans , Infant, Newborn , Infant , Child, Preschool , CD4-Positive T-Lymphocytes/immunology , Killer Cells, Natural/pathology , HIV/pathogenicity , AIDS Serodiagnosis/standards , Serologic Tests/standards , Acquired Immunodeficiency Syndrome/immunology , CD4-Positive T-Lymphocytes/pathology , Dendritic Cells/pathology , Killer Cells, Natural/immunology , HIV/immunology , Immune System/cytology , Immune System/immunology , Immune System/physiopathologyABSTRACT
El virus de la inmunodeficiencia humana (HIV) es un retrovirus, que exhibe tropismo selectivo por células del sistema inmunológico. Tiene acceso al interior celular mediante la molécula CD4, presente fundamentalmente sobre los linfocitos T colaboradores. La unión se da por interacción entre el CD4 y una glicoproteína de la cápside viral, la gp120. La infección de la célula es irreversible, ya que el material genético viral se incorpora, en forma de provirus, el genoma de la célula huésped, donde puede permanecer en estado latente durante un período de tiempo que varía entre unos meses y varios años. La activación del provirus se da en forma conjunta con la activación celular, lleva a la producción elevada de partículas virales. El hecho más significativo es la disminución de células T CD4+ atribuido, al menos en parte, al efecto citopático del virus. De la población total de linfocitos CD4+, solo un pequeño número es susceptible de infección viral, lo cual dificulta la interpretación de su marcada disminución. Teniendo en cuenta que el blanco preferido del virus es una célula central dentro del sistema inmune, puede comprenderse la amplia gama de alteraciones inmunológicas, que presentan los individuos infectados, que lleva a la severa inmunodeficiencia observada en los pacientes con SIDA