Background: CD8 T lymphocytes are critical in the control of HIV replication and disease progression. Our previous studies demonstrated that CD8 T cells from chronically infected patients with high virus load proliferated poorly in response to interleukin-2 (IL-2), a cytokine critical in CD8 T cell growth and differentiation, even though relatively high levels of IL-2 receptor (IL-2R) were expressed. This suggested that signal transduction defects in response to IL-2 might be involved. The STAT5 transcription factor is important in IL-2-dependent biological responses and it is known that there are defects in unstimulated CD3 and CD4 cells in HIV-infected patients.

Objective: To investigate whether the induction of STAT5 by IL-2 is altered in the CD8 T cells from HIV-positive individuals and the impact of highly active antiretroviral therapy (HAART) on its status.

Methods: CD8 T lymphocytes were purified from the peripheral blood mononuclear cells of HIV-positive patients before and after HAART. Ex vivo IL-2-induced STAT5 activation was evaluated by immunoblotting and electrophoretic mobility shift assays.

Results: CD8 T cells from a subset of untreated HIV-positive patients were unable to activate STAT5a and STAT5b proteins functionally in response to IL-2. This defect was not a result of alterations in IL-2R expression but correlated with an impaired activation of the upstream kinase Jak-3, known to mediate STAT5 activation. Overall, HAART restored Jak/STAT signalling in such patients.

Conclusions: These results further uncover a potential mechanism by which CD8 T cell function is impaired in HIV-infected patients.

Download full-text PDF

Source
http://dx.doi.org/10.1097/00002030-200402200-00007DOI Listing

Publication Analysis

Top Keywords

cd8 lymphocytes
12
hiv-positive patients
12
cd8 cells
12
cd8
8
antiretroviral therapy
8
cd8 cell
8
response il-2
8
cells hiv-positive
8
stat5 activation
8
stat5
5

Similar Publications

Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.

View Article and Find Full Text PDF

: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.

View Article and Find Full Text PDF

Dendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74).

View Article and Find Full Text PDF

Background: Programmed cell death ligand 1 (PD-L1) expression on immune cells is correlated with the efficacy of immune checkpoint inhibitor (ICI) therapy in various types of cancer. Platelets are important components of the tumour microenvironment (TME) and are widely involved in the development of many types of cancer including colorectal cancer (CRC). However, the role of PD-L1 positive platelets in ICI therapy for CRC remains unknown.

View Article and Find Full Text PDF

Background: Mycobacterium bovis BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 billion people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and parenteral. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!