Regulation of CD8+ T-cell cytotoxicity in HIV-1 infection

Saeidi, Alireza; Buggert, Marcus; Karlhans, F.; Kong, Yek-Ching; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki Muthu

doi:10.1016/j.cellimm.2015.10.009

Cited by 20 publications

(11 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perforin, a calcium-dependent pore-forming protein, is released in the presence of Ca 2+ and aggregates to form pores on target cell membranes. Granzyme B enters the target cell through these pores and cleaves specific substrates to initiate DNA fragmentation and apoptosis [ 22 ]. In multiple studies of autoimmune diseases, such as multiple sclerosis, CTLs were found to express increased levels of perforin and granzyme B [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

Liu

Zheng

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow failure is mediated by activated myeloid dendritic cells (mDCs) and T lymphocytes. Recent research has identified a strong immunomodulatory effect of pyruvate kinase M2 (PKM2) on dendritic cells in immune-mediated diseases. In this study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared to normal controls at both the gene and protein levels. Concurrently, we unexpectedly discovered that after the mDC-specific downregulation of PKM2, mDCs from patients with SAA exhibited weakened phagocytic activity and significantly decreased and shortened dendrites relative to their counterparts from normal controls. The expression levels of the costimulatory molecules CD86 and CD80 were also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs reduced the abilities of these cells to promote the activation of CD8+ T cells (CTLs), leading to the decreased secretion of cytotoxic factors by the latter cell type. These findings demonstrate that mDC activation requires an elevated intrinsic PKM2 level and that PKM2 improves the immune status of patients with SAA by enhancing the functions of mDCs and, consequently, CTLs.

show abstract

Section: Discussionmentioning

confidence: 99%

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

Liu

Zheng

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…However, the underlying transcriptional mechanisms remain elusive for the most part. Numerous transcription factors have been described to play crucial roles in cytotoxic lymphocyte differentiation, including T-bet, Notch proteins, Runt-related transcription factor 3, B lymphocyte-induced maturation protein-1, the transcriptional repressor Bcl-6, and STAT proteins (24). How the TB proteins influence those transcription factors that control the expression of cytotoxic molecules such as perforin and granzymes remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of perforin in CD8+ T lymphocytes in patients with Mycobacterium tuberculosis infection and its potential value as a marker for efficacy of treatment

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The cellular immune response is critical in controlling the viral replication of HIV-1 (6)(7)(8). The majority of circulating CD8 + T cells in healthy individuals are naïve and central memory cells.…”

Section: Discussionmentioning

confidence: 99%

“…The CD4/CD8 ratio has been reported to be a useful marker for clinical outcome, immune dysfunction and viral reservoir size in HIV-1-infected patients (4,5). Cytotoxic T lymphocytes (CTLs), the critical effector CD8 + T cells, are vital in host defense against HIV-1 by impeding viral replication through cytolytic and non-cytolytic pathways (6). The dynamics of effector CD8 + T cell expansion in acute HIV-1 infection is similar to that in other viral infections (7).…”

Section: Introductionmentioning

confidence: 99%

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Jin

Cheng

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

The differentiation and response ofCD8+ T cells is vital in host defense against human immunodeficiency virus type 1 (HIV-1). MicroRNA (miR)‑155 is an important regulator of T cell differentiation. However, the profile of miR-155 in HIV‑1 infected individuals and its association with CD8+ T cell differentiation remain to be fully elucidated. The present cross‑sectional study was performed involving 63 HIV‑1‑infected patients undergoing highly active antiretroviral therapy (HAART), 31 HAART‑naïve patients and 35 healthy controls. The levels of miR‑155 in CD8+ T cells were detected using reverse transcription‑quantitative polymerase chain reaction analysis. Subsets of CD8+ T cell differentiation were detected using flow cytometry. The results revealed that the discord controllers and HAART‑naïve patients showed higher percentages of effector and effector memory cells, and lower percentages of naïve cells (P<0.05). The levels of miR‑155 in CD8+ T cells from the HIV‑1‑infected patients were higher, particularly in the discord controllers and HAART naïve patients (P<0.01). The expression levels of miR‑155 were positively correlated with the percentages of effector and effector memory CD8+ T cells, and negatively correlated with the percentages of naïve and central memory CD8+ T cells (P<0.01). Taken together, these findings suggested that the levels of miR‑155 in CD8+ T cells of patients with HIV-1 were increased and asso-ciated with CD8+ T cell differentiation.

show abstract

Regulation of CD8+ T-cell cytotoxicity in HIV-1 infection

Cited by 20 publications

References 151 publications

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

Decreased expression of perforin in CD8+ T lymphocytes in patients with Mycobacterium tuberculosis infection and its potential value as a marker for efficacy of treatment

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Contact Info

Product

Resources

About