CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

Abstract

Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8؉ T cells play a critical role in combating HTNV infections. However, the contributions of different CD8 ؉ T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8 CD8 T cells play a critical role in combating viral infections. Dramatic cellular changes occur as T cells transition through the following three characteristic phases of an antiviral response: initial activation and expansion, the death phase, and the formation of memory T cells. However, many aspects of these activation and differentiation processes are inadequately understood, particularly in humans. There are several important cell surface molecules that regulate the interactions between immune cells and, moreover, characterize cell differentiation and activation status.Sema4D, also called CD100, was the first immune semaphorin discovered (1) and is involved in several aspects of both humoral and cellular immunity (2-6). CD100 exists in both a membranebound form and a soluble form. Membrane-associated CD100 is expressed preferentially on T cells and weakly on B cells and antigen-presenting cells (APCs) (2, 7). CD72, the receptor for CD100, is expressed primarily on immune system cells and is present on the surface of most APCs and B cells. Interaction between CD72 and CD100 leads to dendritic cell (DC) maturation and cytokine production and enhances B cell activation (7).Because of the involvement of CD100 in the immune response, we hypothesized that CD100 may play an important role in the antiviral CD8 T cell response. However, there is limited information available regarding the role of CD100 in infectious diseases. Eriksson et al. (8) investigated the effects of HIV-1 infection on CD100 expression in T cells, and they observed that a subset of CD8 ϩ T cells lacking membrane-associated CD100 showed decreased functional capacity. Their findings suggested that loss of CD100 expression would most likely lead to dysfunctional immunity in HIV-1 infection. It is well accepted that there are many differences between acute infections and chronic infections. Acute infections usually result in effective antiviral immune responses, while chronic infections are often associated with suboptimal T cell function. Furthermore, HIV infects CD4 ϩ T cells and B cells and has profound pathological effects on the immune system, further confounding the interpretation of T cell dynamics following the acute phase. Therefore, it is important to investigate the functional role of CD100 in the CD8 antiviral response in acute infections.

PI3K Inhibition Reduces Mammary Tumor Growth and Facilitates Antitumor Immunity and Anti-PD1 Responses

“…We performed neutrophil chemotaxis assays (CXCL8 ligand, 0, 30, 300 ng/ml) in the presence or absence of BKM120 ( 0–1000nM) and as expected from our prior work, the migration of neutrophils isolated from mouse bone marrow was not significantly affected by PI3K inhibition (Figure 1 E) [33, 34]. To determine how BKM120 treatment affected tumor cell migration and invasion, we performed in vitro transwell invasion assays.…”

CD8low T cells expanded following acute Trypanosoma cruzi infection and benznidazole treatment are a relevant subset of IFN-γ producers

“…In fact, some studies have shown that a proportion of CD8 + T cells displays low surface expression of the CD8 molecule after viral infections [27][28][29]. During the early phase of human Hantaan virus (HTNV) infection, CD8 low cells expressed high levels of cytolytic effector molecules and were associated with high activation status, exhibiting an effector phenotype as CCR7 +/-CD45RA -CD127 high CD27 int CD28 low CD62L low [30]. This study also revealed these cells as the main producers of IFN-γ and TNF among CD8 + T cells, when stimulated with specific HTNV peptides.…”

Hantavirus-Driven PD-L1/PD-L2 Upregulation: An Imperfect Viral Immune Evasion Mechanism

“…Other investigators detected increased amounts of PD-L1 in hantavirus-infected cultures of rat endothelial cells (80). In HFRS patients, hantavirus-induced PD-L1 may be responsible for the contraction of a newly identified highly cytotoxic T cell subset that strongly upregulates PD-1 in the late phase of hantavirus infection (81). Hantavirus-induced expression of PD-L1 and PD-L2 may contribute to the recently described protection of hantavirus-infected endothelial cells from cytotoxic attack by CD8+ T cells and NK cells (82).…”