NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

Abstract

Introduction. NKT-like cells are "non-classical", "CD1d-independent" NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing. Material and methods. The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess NKT-like (CD3+CD56+) and T (CD3+) cell populations. Results. The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable. Conclusions. The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression

“…HSP70 is not immunogenic but can participate in antigen processing after binding to polypeptides and enhance the immune response. A clinical trial injected purified HSP70 into children with brain cancer and found an antitumor effect and certain feasibility and safety in the antitumor therapy [54,55]. Another study has also shown that HSP70 inhibits brain tumor development in a C6 glioblastoma mouse model, which is associated with NK cell and T lymphocyte killing abilities of glioblastoma, as well as increased activities of NK cells and CD81 + T lymphocytes [55].…”

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression

“…Previous studies have shown that HSP70 is not immunogenic but can participate in antigen processing after binding to polypeptides and enhance the immune response. A clinical trial injected puri ed HSP70 into children with brain cancer and found an antitumor effect and certain feasibility and safety in the antitumor therapy [52,53]. Another study has also shown that HSP70 inhibits brain tumor development in a C6 glioblastoma mouse model, which is associated with NK cell and T lymphocyte killing abilities of glioblastoma, as well as increased activities of NK cells and CD81 + T lymphocytes [53].…”

“…A clinical trial injected puri ed HSP70 into children with brain cancer and found an antitumor effect and certain feasibility and safety in the antitumor therapy [52,53]. Another study has also shown that HSP70 inhibits brain tumor development in a C6 glioblastoma mouse model, which is associated with NK cell and T lymphocyte killing abilities of glioblastoma, as well as increased activities of NK cells and CD81 + T lymphocytes [53]. In the present study, we found that metformin increased HSF-1, MICA and HSP70 protein expression in SiHa and HeLa cells and also induced MICA expression on the surface of human cervical cancer cells.…”

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression

“…HSP70 is not immunogenic but can participate in antigen processing after binding to polypeptides and enhance the immune response. A clinical trial injected puri ed HSP70 into children with brain cancer and found an antitumor effect and certain feasibility and safety in the antitumor therapy [54,55]. Another study has also shown that HSP70 inhibits brain tumor development in a C6 glioblastoma mouse model, which is associated with NK cell and T lymphocyte killing abilities of glioblastoma, as well as increased activities of NK cells and CD81 + T lymphocytes [55].…”

“…A clinical trial injected puri ed HSP70 into children with brain cancer and found an antitumor effect and certain feasibility and safety in the antitumor therapy [54,55]. Another study has also shown that HSP70 inhibits brain tumor development in a C6 glioblastoma mouse model, which is associated with NK cell and T lymphocyte killing abilities of glioblastoma, as well as increased activities of NK cells and CD81 + T lymphocytes [55]. In the present study, we found that metformin increased HSF-1, MICA and HSP70 protein expression in SiHa and HeLa cells and also induced MICA expression on the surface of human cervical cancer cells.…”