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Self-antigen-specific T cells are prevalent in the mature adaptive immune system but are regulated through multiple mechanisms of tolerance. However, inflammatory conditions such as tissue injury may allow these T cells to break tolerance and trigger autoimmunity. To understand how the T cell repertoire responds to the presentation of self-antigen under highly stimulatory conditions, we use peptide:major histocompatibility complex (MHC) class II tetramers to track the behavior of endogenous CD4 + T cells with specificity to a lung-expressed self-antigen in mouse models of immune-mediated lung injury. Acute injury results in the exclusive expansion of CD4 + regulatory T cells (Tregs) that is dependent on self-antigen recognition and interleukin-2 (IL-2). Conversely, conventional CD4 + T cells of the same self-antigen specificity remain unresponsive even following Treg ablation. Thus, the self-antigen-specific CD4 + T cell repertoire is poised to serve a regulatory function during acute tissue damage to limit further damage and the possibility of autoimmunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

HIV-1 entry into host cells leads to one of the following three alternative fates: (1) HIV-1 elimination by restriction factors, (2) establishment of HIV-1 latency, or (3) active viral replication in target cells. Here, we report the development of an improved system for monitoring HIV-1 fate at single-cell and population levels and show the diverse applications of this system to study specific aspects of HIV-1 fate in different cell types and under different environments. An analysis of the transcriptome of infected, primary CD4+ T cells that support alternative fates of HIV-1 identifies differential gene expression signatures in these cells. Small molecules are able to selectively target cells that support viral replication with no significant effect on viral latency. In addition, HIV-1 fate varies in different tissues following infection of humanized mice in vivo. Altogether, these studies indicate that intra- and extra-cellular environments contribute to the fate of HIV-1 infection., Competing Interests: Declaration of interests A.N.E. has received fees from ViiV Healthcare, Co. for consultancy services unrelated to this work. The other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many HIV strains downregulate the levels of CD4 receptor on the surface of infected cells to prevent superinfection. In contrast, the rare HIV-2 UC1 strain is noncytopathic and has no effect on CD4 expression in infected cells but still replicates as efficiently as more cytopathic strains in peripheral blood mononuclear cells (PBMCs). Here, we show that HIV-2 UC1 Env interactions with the CD4 receptor exhibit slow association kinetics, whereas the dissociation kinetics is within the range of cytopathic strains. Despite the resulting 10- to 100-fold decrease in binding affinity, HIV-2 UC1 Envs exhibit long-lived activation state and efficient fusion activity. These observations suggest that HIV-2 UC1 Envs evolved to balance low affinity with an improved and readily triggerable molecular machinery to mediate entry. Resistance to cold exposure, similar to many primary HIV-1 isolates, and to sCD4 neutralization suggests that HIV-2 UC1 Envs preferentially sample a closed Env conformation. Our data provide insights into the mechanism of HIV entry., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)