CTLA4
Cytotoxic T-lymphocyte protein 4 precursor (Cytotoxic T-lymphocyte-associated antigen 4) (CTLA-4) (CD152 antigen) [CD152]
Publications[править]
With the challenges that aging populations pose to healthcare, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of Horticultural Therapy (HT). We aimed to examine the effects of HT on immunosenescence. We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over six months. Venous blood was drawn at baseline and at the 3 rd and 6 th month from the commencement of this study. For participants who attended all three blood collection time points (HT: n=22, waitlist: n=24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4 and CD8 subsets expressing exhaustion markers - CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels. HT is associated with increased numbers of naïve CD8 T cells and fewer CTLA4-expressing terminally differentiated effector CD4 and CD8 memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8 T cells were found to be associated with IL-6 levels. HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustionwere associated with the reduction of IL-6 levels.
Keywords
- CTLA-4
- Geroscience
- IL-6
- Immunosenescence
- Inflammaging
Physiological aging causes qualitative or quantitative immune system decline, also called immunosenescence. Older people with cancer are often ineligible for chemotherapy. The new immunotherapies (with PD1, PDL1 and CTLA4 checkpoint inhibitors) have proven their effectiveness in many tumor types regardless of age and are often better tolerated than chemotherapy. In the older population, the subgroup data from the different pivotal studies show fairly reassuring efficacy and safety data, despite the frequent lack of power given the small population included. There remains, however, some doubt that age may be a risk factor for hyperprogression. Studies focusing on older subjects and dedicated meta-analysis seem necessary to obtain more accurate data.
MeSH Terms
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Immunological
- B7-H1 Antigen
- CTLA-4 Antigen
- Humans
- Immunosenescence
- Immunotherapy
- Neoplasms
- Nivolumab
- Programmed Cell Death 1 Receptor
Keywords
- Adverse event
- Efficacité
- Efficacy
- Elderly people
- Immune checkpoint inhibitors
- Inhibiteurs de points de contrôle immuns
- Personnes âgées
- Tolérance
The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4 CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6 CCR4 CXCR3 , and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3 /interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4 CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.
MeSH Terms
- Adult
- Aged
- Aging
- Antigens, Differentiation, T-Lymphocyte
- Arthritis, Rheumatoid
- Case-Control Studies
- Cytokines
- Disease Progression
- Female
- Flow Cytometry
- Gene Expression Profiling
- Humans
- Immunophenotyping
- Lymphocyte Count
- Male
- Middle Aged
- Receptors, CXCR3
- T-Lymphocyte Subsets
- T-Lymphocytes, Helper-Inducer
- T-Lymphocytes, Regulatory
- Transcription Factors
Keywords
- T cell profile
- autoimmunity
- chemokine receptors
- multivariate discriminant analysis