scholarly journals Evaluation of T cell responses in healing and nonhealing leishmaniasis reveals differences in T helper cell polarizationex vivoandin vitro

2009 ◽  
Vol 31 (4) ◽  
pp. 199-209 ◽  
Author(s):  
B.-S. CHOI ◽  
P. KROPF
Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2365
Author(s):  
Christina E. Zielinski

T helper cell responses are tailored to their respective antigens and adapted to their specific tissue microenvironment. While a great proportion of T cells acquire a resident identity, a significant proportion of T cells continue circulating, thus encountering changing microenvironmental signals during immune surveillance. One signal, which has previously been largely overlooked, is sodium chloride. It has been proposed to have potent effects on T cell responses in the context of autoimmune, allergic and infectious tissue inflammation in mouse models and humans. Sodium chloride is stringently regulated in the blood by the kidneys but displays differential deposition patterns in peripheral tissues. Sodium chloride accumulation might furthermore be regulated by dietary intake and thus by intentional behavior. Together, these results make sodium chloride an interesting but still controversial signal for immune modulation. Its downstream cellular activities represent a potential therapeutic target given its effects on T cell cytokine production. In this review article, we provide an overview and critical evaluation of the impact of this ionic signal on T helper cell polarization and T helper cell effector functions. In addition, the impact of sodium chloride from the tissue microenvironment is assessed for human health and disease and for its therapeutic potential.


1983 ◽  
Vol 157 (1) ◽  
pp. 312-323 ◽  
Author(s):  
A Bandeira ◽  
G Pobor ◽  
S Petterson ◽  
A Coutinho

Major histocompatibility complex-restricted helper T cell clones against "minor" antigens expressed on B cell and macrophage surfaces, when confronted with appropriate T cell-depleted spleen cells, are induced to proliferation and, in turn, activate "target-responder" B cells to polyclonal growth and maturation. Irradiation of helper cell populations, however, demonstrates that their effector functions (and B lymphocyte responses) are independent of proliferative activity. Adherent cell depletion on Sephadex G10 columns, while completely abrogating helper T cell proliferation, does not abolish helper cell-induced B cell responses, demonstrating a remarkable quantitative difference in macrophage requirements for the growth of these two cell types. Because significant B cell responses are detected upon interaction with primed helper T cells under conditions of extreme macrophage depletion, we conclude that the role of macrophages in T-B cell cooperation is limited to expansion of optimal numbers of helper T lymphocytes. It follows that activated helper cells can autonomously produce all B cell-specific growth and maturation factors mediating cooperative antibody responses. In contrast, the profound reduction of LPS-induced responses upon macrophage depletion suggests accessory cell production of such factors in thymus-independent B cell growth and/or maturation.


Nature ◽  
2021 ◽  
Author(s):  
Michael Platten ◽  
Lukas Bunse ◽  
Antje Wick ◽  
Theresa Bunse ◽  
Lucian Le Cornet ◽  
...  

AbstractMutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1–3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6–8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634). The trial met its primary safety endpoint, with vaccine-related adverse events restricted to grade 1. Vaccine-induced immune responses were observed in 93.3% of patients across multiple MHC alleles. Three-year progression-free and death-free rates were 0.63 and 0.84, respectively. Patients with immune responses showed a two-year progression-free rate of 0.82. Two patients without an immune response showed tumour progression within two years of first diagnosis. A mutation-specificity score that incorporates the duration and level of vaccine-induced IDH1(R132H)-specific T cell responses was associated with intratumoral presentation of the IDH1(R132H) neoantigen in pre-treatment tumour tissue. There was a high frequency of pseudoprogression, which indicates intratumoral inflammatory reactions. Pseudoprogression was associated with increased vaccine-induced peripheral T cell responses. Combined single-cell RNA and T cell receptor sequencing showed that tumour-infiltrating CD40LG+ and CXCL13+ T helper cell clusters in a patient with pseudoprogression were dominated by a single IDH1(R132H)-reactive T cell receptor.


1993 ◽  
Vol 67 (6) ◽  
pp. 3680-3683 ◽  
Author(s):  
T M Kündig ◽  
I Castelmur ◽  
M F Bachmann ◽  
D Abraham ◽  
D Binder ◽  
...  

AIDS ◽  
2003 ◽  
Vol 17 (8) ◽  
pp. 1121-1126 ◽  
Author(s):  
Gregory K Robbins ◽  
Marylyn M Addo ◽  
Hien Troung ◽  
Almas Rathod ◽  
Kathy Habeeb ◽  
...  

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