RESUMEN
We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8+ T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8+ T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4+ T cells abrogated, whereas adoptive transfer of Ag-specific CD4+ T cells induced the significant reduction of Ag-specific CD8+ T cell TNF-α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediate early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.
Asunto(s)
Vacunas Bacterianas , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Infecciones por Chlamydia , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por Chlamydia/inmunología , Infecciones por Chlamydia/prevención & control , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Femenino , Ratones , Modelos Animales de Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Chlamydia muridarum/inmunologíaRESUMEN
We highlight a novel case of TAFRO syndrome with disseminated intravascular coagulation, neurologic changes, and non-ischemic cardiomyopathy. Through this clinical vignette, we hope to raise awareness of TAFRO syndrome and encourage providers to maintain a high level of suspicion for it when evaluating patients who meet the diagnostic criteria.
RESUMEN
Amyloidosis is a rare disease that involves the extracellular deposition of abnormally folded proteins, precipitating organ dysfunction. Pulmonary amyloidosis is frequently characterized by the AL amyloid subtype and can be localized or associated with systemic involvement, presenting in a nodular, diffuse alveolar-septal, or tracheobronchial pattern. Presentation of disease can vary from clinically silent to severe. Pulmonary amyloidosis is typically first suspected on CT scan of the chest. Diagnostic workup requires tissue biopsy and identification by immunohistochemical staining. Systemic treatment has evolved over recent years to include the combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone (dara-VCD) as first-line therapy, with the goal of quickly attaining complete hematologic response. Through clinical vignettes, we review pulmonary AL amyloidosis and discuss current treatment options.