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In systemic lupus erythematosus, immune complexes deposited in the kidney vasculature represent a potent inflammatory trigger with a high potential to progress to glomerulonephritis and organ failure. These immune complexes can be recognized by multiple effector cells via complement and Fcγ receptors. The transcriptome of CD16-bearing NK cells has been documented in kidneys from patients with SLE. In this study, we show that NK cells accumulate in the kidney in response to immune complex deposition and modulate the behavior of local T cells. Depletion of NK cells transiently ameliorated disease, suggesting NK cells may play a role in lupus nephritis and other immune complex-mediated conditions. [ABSTRACT FROM AUTHOR]

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55[beta], a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated [CD8.sup.+] T cells. Through the modulation of AKT, B55[beta] induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55[beta] and Hrk were both required for in vivo and in vitro contraction of activated [CD8.sup.+] lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory., Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that regulates a large number of cellular processes, including apoptosis (1). PP2A is ubiquitously expressed, and defects in its activity and/or expression [...]

Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-γ but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-γ and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically., (Copyright © 2024 by The American Association of Immunologists, Inc.)