Systemic Cancer Immunostimulatory Therapies and Acute Viral Infection Induce Corticosteroid-Mediated Thymic Involution and Naïve T cell Output in Mice and Humans

Abstract Thymic involution (TI) occurs with aging and during stress responses, decreasing naïve T cell output. progenitor apoptosis can occur directly by corticosteroids (CS) leading to transient followed recovery. The effects of systemic immunotherapies (IT) used in cancer or immune stimulation via acute viral infection on the thymus has not been well-characterized was primary goal this study. IT treatment mice high dose IL-2 (HD IL-2) models (mouse cytomegalovirus, MCMV) all resulted rapid TI due CD4/CD8 double-positive progenitors a reduction content. Interestingly, cessation therapy resolution greater thymic size compared untreated recipients, indicating rebound effect. In both models, increased CS levels serum preceded TI. Clinically, patients receiving HD for had significantly reduced receptor excision circles, marker output, also correlating cortisol levels. Using model sub-lethal MCMV that did increase pro-inflammatory cytokines, we observed similar correlation To further analyze TI, were adrenalectomized then given IL-2, where correlated partial protection from These results indicate strong immunostimulation either infections markedly induce CS-mediated decrease cells. Therefore, targeting responses preventing and, especially aged, allow populations be maintained.