ABSTRACT
SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract and a vast proportion secrete the cytotoxic molecule Granzyme B. Using antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.
ABSTRACT
BACKGROUND AND AIMS: Evidence assessing the role of B cells and their antibodies, or lack thereof, in the spontaneous resolution of acute HCV infection is conflicting. Utilization of a strictly hepatotropic, HCV-related rodent hepacivirus (RHV) model circumvents many of the challenges facing the field in characterizing the immunological correlates of dichotomous infection outcomes. This study seeks to elucidate the importance of B cells in the clearance of acute RHV infection. APPROACH AND RESULTS: µMT mice were infected i.v. with RHV and found to develop chronic infection for over a year. Wild-type (WT) mice depleted of B cells also exhibited persistent viremia that resolved only upon B cell resurgence. The persistent infection developed by B1-8i and AID cre/cre mice revealed that antigen-specific, class-switched B cells or their antibodies were crucial for viral resolution. Virus-specific CD8 + and CD4 + T cells were characterized in these mice using newly developed major histocompatibility complex class I and II tetramers and ex vivo peptide stimulation. Immunoglobulin G (IgG) was purified from the serum of RHV- or lymphocytic choriomeningitis virus Armstrong-infected mice after viral clearance and passively transferred to AID cre/cre recipients, revealing viral clearance only in αRHV IgG recipients. Further, the transfer of αRHV IgG into B cell-depleted recipients also induced viral resolution. This ability of RHV-specific IgG to induce viral clearance was found to require the concomitant presence of CD8 + T cells. CONCLUSIONS: Our findings demonstrate a cooperative interdependence between immunoglobulins and the T cell compartment that is required for RHV resolution. Thus, HCV vaccine regimens should aim to simultaneously elicit robust HCV-specific antibody and T cell responses for optimal protective efficacy.
ABSTRACT
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Subject(s)
Humans , Aspirin/therapeutic use , Myocardial Ischemia/drug therapy , Acute Coronary Syndrome/drug therapy , Thrombosis/prevention & control , Desensitization, Immunologic , Aspirin/adverse effects , Drug Hypersensitivity/therapyABSTRACT
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Subject(s)
Adult , Male , Humans , Morals , Counseling , Streptokinase , Thrombosis , Thromboembolism , Venous Thrombosis , Ear Diseases , Eustachian Tube , Fibrinolytic AgentsABSTRACT
Se realizó un estudio clínico estrospectivo longitudinal de 50 pacientes con fractura inestable de tobillo tratados con el método AO-ASIF. Con seguimiento de 12.8 meses los resultados fueron satisfactorios en 90 por ciento. Obtuvimos 78 por ciento de fracturas B de Weber, 18 por ciento C y 4 por cieto A con ruptura de la sindesmosis que se trató con tornillo de situación de 4.5 , sin permitir la descarga hasta su retiro. Se estabilizó de maléolo lateral en 82 por ciento de los casos con placa de 1/3 de caña y tornillos interfragmentarios manteniendo la longitud del peroné primordialmente. El ligamento deltoideo se reparó en 18 por ciento de los casos. Todas las fracturas del maléolo posterior mayores del 25 por ciento se redujeron quirúrgicamente (14 por ciento de los casos). Se obtuvo una reducción de 93.5 por ciento en el tratamiento quirúrgico de las fracturas del tobillo y se comprobó que hasta 2 mm de desplazamiento del maléolo lateral, medial o ambos conducen aún a resultados satisfactorios. En tres pacientes se infectó la herida quirúrgica y uno de ellos desarrolló artrosis a los seis meses, uno más tuvo dehiscencia de la herida y dos se reintervinieron para realinear el maléolo medial. La función en cuanto a movilidad y marcha fue satisfactoria después de la estabilización quirúrgica de la fractura
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Ankle/surgery , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Bone Screws , Ankle/injuries , Fractures, Bone/classificationABSTRACT
Hemos comparado las prevalencias de grupos sanguíneos entre los pacientes que acudieron al Servicio de Emergencia del Hospital Nacional Cayetano Heredia (Lima, Perú) durante el mes de abril de 1991 con diarrea aguda severa con aislamiento de Vibrio cholerae en los coprocultivos, con la de un grupo control conformado por los donantes del Banco de Sangre del mismo hospital, apareados por distritos de residencia. La prevalencia de grupo sanguíneo O entre los 136 pacientes con coprocultivo positivo (todos a V. cholerae o1 biotipo El Tor serotipo Inaba) fue de 94.9 por ciento mientras que en los 544 controles fue de 79.2 por ciento (similar a la reportada en otros estudios sobre prevalencia de grupos sanguíneos en nuestra población). Aunque el diseño del estudio tiende a subestimar el real riesgo relativo, encontramos un riesgo relativo estimado de 4.832 (IC95=2.196, 10.628) de presentar diarrea aguda severa por V.cholerae entre las persona con grupo sanguíneo O (p<0.00002). Queda por descubrir la base fisiopatológica de esta asociación y el impacto que puede tener en la morbilidad y mortalidad de la presente epidemia de cólera en el Perú, país con alta prevalencia de grupo sanguíneo O