RESUMO
Regulatory T cells (Treg) play critical roles in the modulation of immune responses to infectious agents. Further understanding of the factors that control Treg activation and expansion in response to pathogens is needed to manipulate Treg function in acute and chronic infections. Here we show that chronic, but not acute, infection of mice with lymphocytic choriomeningitis virus results in a marked expansion of Foxp3(+) Treg that is dependent on retroviral superantigen (sag) genes encoded in the mouse genome. Sag-dependent Treg expansion was MHC class II dependent, CD4 independent, and required dendritic cells. Thus, one unique mechanism by which certain infectious agents evade host immune responses may be mediated by endogenous Sag-dependent activation and expansion of Treg.
Assuntos
Retrovirus Endógenos/imunologia , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/imunologia , Superantígenos/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Animais , Proliferação de Células , Doença Crônica , Células Dendríticas/citologia , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Vírus do Tumor Mamário do Camundongo/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
The production of antibody-secreting plasma cells and memory B cells requires the interaction of T follicular helper (Tfh) cells with B cells in the follicle and is modulated by T follicular regulatory (Tfr) cells. We compare the effects of Tfr cells in an in vitro model of bystander Tfh function in the absence of BCR engagement and in a model in which mimics cognate T-B interactions in which the BCR is engaged. In the absence of Tfr cells, Tfh cells from primed mice induce naive B cell differentiation into GC B cells and class switch recombination (CSR) in the presence of anti-CD3 alone or anti-CD3/IgM in a contact-dependent manner. Addition of primed Tfr cells efficiently suppressed GC B cell proliferation, differentiation and CSR in the anti-CD3 alone cultures, but only moderately suppressed BCR-stimulated B cells. When stimulated with anti-CD3 alone, IL-4 is critical for the induction of GC B cells and CSR. IL-21 plays a minimal role in GC B cell differentiation, but a greater role in switching. When the BCR is engaged, IL-4 is primarily required for switching and IL-21 only modestly affects switching. CD40L expression was critical for Tfh-mediated B cell proliferation/differentiation in the absence of B cell engagement. When the BCR was engaged, proliferation of CD40 deficient B cells was partially restored, but was susceptible to suppression by Tfr. These studies suggest that in vitro Tfr suppressor function is complex and is modulated by BCR signaling and CD40-CD40L interactions.
Assuntos
Linfócitos B/imunologia , Antígenos CD40/metabolismo , Centro Germinativo/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos CD40/genética , Comunicação Celular , Células Cultivadas , Interleucina-4/metabolismo , Interleucinas/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de SinaisRESUMO
BACKGROUND: Aerobic exercise training is associated with beneficial ventricular remodeling and an improvement in cardiac biomarkers in chronic stable heart failure. High-intensity interval training (HIIT) is a time-efficient method to improve V Ë O 2 peak in stable coronary heart disease patients. This pilot study aimed to compare the effect of HIIT on ventricular remodeling in patients with a recent acute myocardial infarction (AMI). METHODS: Nineteen post-AMI patients were randomized to either HIIT (n = 9) or usual care (n = 10). A cardiopulmonary exercise test (CPET), transthoracic echocardiography, and cardiac biomarker assessment (ie, N-terminal pro B-type natriuretic peptide levels and G protein-coupled receptor kinase 2 expression) were performed before and after a 12-week training intervention. CPET parameters including oxygen uptake efficiency slope (OUES) and V Ë O 2 at the first ventilatory threshold ( V Ë O 2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. RESULTS: V Ë O 2 peak and OUES improved solely in the HIIT group (P < .05 for group/time, respectively). There was a significant training effect for the improvement of peak work load in both groups (P < .05). O2 pulse and V Ë O 2 at VT1 both improved only in the HIIT group (P < .05 for time, no interaction). HIIT improved radial strain and pulsed-wave tissue Doppler imaging derived e' (P < .05 for time, no interaction). Cardiac biomarkers did not change in either group. CONCLUSIONS: In post-AMI patients, HIIT lead to significant improvements in prognostic CPET parameters compared to usual care. HIIT was associated with favorable ventricular remodeling regarding certain echocardiographic parameters of LV function.