Antibody Responses to T-Dependent Antigens: Contributions of Dendritic Cells and Helper T Lymphocytes

Author(s):  
Kayo Inaba ◽  
Ralph M. Steinman
2021 ◽  
Vol 19 ◽  
Author(s):  
Giovana Toledo Alonso ◽  
Denilson Stork Fomin ◽  
Luiz Vicente Rizzo

1987 ◽  
Vol 165 (2) ◽  
pp. 515-530 ◽  
Author(s):  
S L Koide ◽  
K Inaba ◽  
R M Steinman

The function of exogenous murine recombinant IL-1 alpha as a T lymphocyte-activating molecule was examined. IL-1 did not induce IL-2 release or responsiveness in purified T cells regardless of their state of activation: unprimed lymphocytes, freshly sensitized lymphocytes, or memory cells derived from the blasts. Nor did IL-1 synergize with mitogens, or with antigens, to stimulate proliferation. For example the combinations of IL-1 plus Ia+ peritoneal macrophages, or IL-1 plus Con A, were less than 5% as effective in triggering T cell growth as a low dose (1%) of dendritic cells. However, when IL-1 was added at the onset of culture, the response to limiting doses of dendritic cells was increased 3- to 10-fold in several systems: the syngeneic and allogeneic MLR, Con A- and periodate-induced polyclonal mitogenesis, and T-dependent antibody formation against foreign red cells. The amplifying effect of IL-1 could be obtained if the dendritic cells but not the responding lymphocytes were exposed to IL-1 before use as accessory cells. Optimal activation of dendritic cells required a dose of 5 U/ml (50 pM) and 18 h of exposure, and was not due to carryover of IL-1 into the lymphocyte culture. IL-2, IL-3, and cachectin/TNF did not amplify dendritic cell function, while IFN-gamma diminished it. The enhanced function of IL-1-treated dendritic cells was due to an enhanced clustering with helper T lymphocytes in the first day of the MLR response. Therefore IL-1 does not seem to act as an activating factor for most peripheral T lymphocytes. Instead, IL-1 enhances the function of accessory dendritic cells and represents the first molecule that has been shown to enhance the immune response at this critical level.


2020 ◽  
pp. 1-10
Author(s):  
Aicha El Allam ◽  
Sara El Fakihi ◽  
Hicham Tahoune ◽  
Karima Sahmoudi ◽  
Houria Bousserhane ◽  
...  

The number of circulating lymphocytes is altered in a number of diseases including either increase (lymphocytosis) or decrease (lymphocytopenia). Therefore, the assessment of total blood lymphocyte numbers and the relative distribution of lymphocyte subsets is a critical front-line tool in the clinical diagnosis of a number of diseases, including pediatric diseases and disorders. However, the interpretation of this data requires comparison of patient’s results to reliable reference values. Blood lymphocyte subpopulation numbers are also subject to genetic polymorphisms, immunogenic and environmental factors and vary greatly between populations. While the best practice reference values should be established within local representative populations of healthy subjects, to date, Caucasian reference values are used in Morocco due to the absence of indigenous reference values. Potential differences in blood lymphocyte subpopulation reference values between Caucasian versus Moroccan populations can adversely affect the diagnosis of pediatric and childhood diseases and disorders such as primary immunodeficiency (PID) in Morocco. OBJECTIVE: The aim of this study was to establish the age-stratified normal reference values of blood lymphocyte subsets for the pediatric Moroccan population. METHODS: We measured the concentration of lymphocyte subpopulations by flow cytometry from 83 Moroccan healthy subjects stratified into 5 age groups of 0–1, 1–2, 2–6, 6–12 and > 12–18 (adult). RESULTS: The absolute and relative amounts of the main lymphocyte subsets of T-cells, B cells and Natural Killer (NK) cells were measured and compared to previously described reference values from Cameroonian, Turkish, American and Dutch populations. Additionally, we also observed an age-related decline in the absolute population sizes of lymphocyte subsets within our study group. Relative proportions of CD3+CD4+ helper T lymphocytes decreased with increasing age and by 12 years-adult age, both proportions of CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, as well as CD3-CD19+ B lymphocytes were also decreased. Finally, we compared the median values and range of our Moroccan study group with that of published results from Cameroon, Turkey, USA and Netherlands and observed significant differences in median and mean values of absolute number and relative proportions of lymphocyte subsets especially at 0–1 years and 1–2 years age groups. Above age 12 years, the Moroccan values were lower. For NK cells, the Moroccan values are also lower. CONCLUSIONS: The results of this study have a significant impact in improving the threshold values of the references intervals routinely used in the diagnosis of paediatric diseases such as PIDs or mother-to-child transmitted HIV within the Moroccan population.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 578.1-579
Author(s):  
S. Schnitte ◽  
A. Fuchs ◽  
T. Funk ◽  
A. C. Pecher ◽  
D. Dörfel ◽  
...  

Background:Psoriasis is a frequent skin disease that can appear with an arthritic manifestation in approximately 30% of the cases [1]. The underlying excessive immune reaction caused by pro-inflammatory cytokines can be triggered by several risk factors [2]. Various subgroups of Dendritic cells (DCs) in the skin play a crucial role in the induction of the dermal inflammatory response [3].Objectives:As the role of peripheral blood DCs remains unknown and the cause of an arthritic manifestation is still not completely understood [4], this project aimed to detect differences in phenotype or function of peripheral blood DCs in psoriatic patients with or without arthritis.Methods:We analyzed peripheral blood cells of 60 psoriasis patients with and without arthritis. Different DC subpopulations were detected by flow cytometry. Monocyte-derived DCs were cultured with or without Lipopolysaccharides to gain immature (iDC) and mature (mDC) cells. The DC phenotype was determined by staining with CD80, CD83, CD86, CD206, CCR7, CD1a, HLA-DR, CD40, GPN-MB, DC209 and CD14. Their T-cell stimulatory capability was analyzed by co-incubation with Carboxyfluorescein succinimidyl ester stained lymphocytes and the quantification of CD4+ T-lymphocytes afterwards. To measure the migration capacity DCs were seated into transwell chambers with a semipermeable membrane and partly supplemented with Macrophage Inflammatory Protein 3 Beta (Mip3b). Migrated cells were detected by flow cytometry. Measured cell counts were normalized to cell counts without Mip3b stimulation.Results:Comparing the factor of increase of migrated mDC counts due to mip3b stimulation, we detected a significant lower rate in samples of patients with arthritis (PsA) compared to those of patients without (Ps). Assays of mDCs without mip3b stimulation showed a significant higher count of migrated cells in the samples of the arthritic group [Figure 1]. Cell counts with Mip3b stimulation did vary slightly in the groups. The DC subpopulations and the expression of analyzed cell surface proteins did not show significant differences. The amounts of stimulated T-Lymphocytes did not differ significantly.Figure 1.Migration essay showing mDCs following Mip3b (+miß3b) as multiples of mDCs without stimulation (-mip3b). The factor of increase is significantly lower in patients with arthritis (PsA) compared to patients without (Ps). Absolute counts of migrated mDCs without Mip3b are significantly higher in the arthritic group. Cell counts with stimulation do not differ significantly (data not shown). N=24, p<0.05Conclusion:CCL19 (Mip3b) is a potent ligand to the CCR7 receptor inducing migration of DCs towards the lymphatic node [5]. The CCR7 amounts on the DC surface did not differ significantly in the groups. The mDCs without CCL19 stimulation migrated in higher amounts in samples of arthritic patients. Cell counts of stimulated DCs showed only slight differences. These results could be generated by a different appearance of the DCs of arthritic patients that might facilitate migration. Further experiments focusing on this aspect should be performed. A possible effect of disruptive factors (age, sex, medication…) needs to be clarified.References:[1]Henes, J.C., et al.,High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study.Rheumatol Int, 2014.34(2): p. 227-34.[2]Lee, E.B., et al.,Psoriasis risk factors and triggers.Cutis, 2018.102(5s): p. 18-20.[3]Kim, T.G., S.H. Kim, and M.G. Lee,The Origin of Skin Dendritic Cell Network and Its Role in Psoriasis.Int J Mol Sci, 2017.19(1).[4]Veale, D.J. and U. Fearon,The pathogenesis of psoriatic arthritis.Lancet, 2018.391(10136): p. 2273-2284.[5]Ricart, B.G., et al.,Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.J Immunol, 2011.186(1): p. 53-61.Acknowledgments:This project was financially supported by Novartis Pharma GmbH.Disclosure of Interests:Sarah Schnitte Grant/research support from: Reaserch grant by Novartis, Alexander Fuchs: None declared, Tanja Funk: None declared, Ann-Christin Pecher: None declared, Daniela Dörfel: None declared, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,


2005 ◽  
Vol 25 (3) ◽  
pp. 230-237 ◽  
Author(s):  
Angelo Martino ◽  
Rita Casetti ◽  
Alessandra D’Alessandri ◽  
Alessandra Sacchi ◽  
Fabrizio Poccia

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