It's a known fact that younger individuals infected with SARS-CoV-2 had fewer cases and a lower mortality rate. Also it's assumed that the human immune system develops continuously from birth to adolescence, and that immunity to infections is strongest in early to middle adulthood, then begins to wane in late age.
Now, a Chinese team of researchers from Sichuan University, hypothesize that Naïve T cells may contribute to lower mortality rates observed. Their explanation as below.
"Naïve T cells retain their specificity by expressing unique T-cell receptors (TCRs) but remain uncommitted to their helper fate until they encounter antigens presented by antigen-presenting cells (APCs). Each naïve T cell moves through the blood to the lymph nodes every 12–24 h, but only 1 in 10 naïve T cells may respond to any given antigen. If naïve T cells do not bind to any APC-presented MHC/antigen complexes, they exit through the thoracic duct and travel back into the blood. Once a naïve T cell encounters the corresponding MHC/antigen complex, it stops circulating, becomes activated, and proliferates and differentiates into effector and memory T cells with identical antigen specificity.
Thus, the number of naïve T cells may be key to assisting the body in identifying and coping with SARS-CoV-2 infections. For everyone, both young and old, this virus is a new pathogen that has never been encountered by their immune system. Therefore, in children's immune systems, there is essentially no difference between SARS-CoV-2 and common pediatric pathogens such as respiratory viruses, enteroviruses, and conditioned pathogenic bacteria. The immune system needs only to recognize it, activate the adaptive immunity, and store the memory T cells, which is not different from the way in which these cells cope with other pathogens. For example, when a child first enters kindergarten, close contact with other children exposes the child to a large number of new pathogens in a short period of time, which may cause the child to be continuously infected by various bacteria or viruses. This process usually lasts for several months, and in some cases, it even lasts for one or two years. Thus, in children, SARS-CoV-2 may not be substantially different from other newly encountered pathogens.
However, after childhood, the number of naïve T cells is significantly reduced, and memory T cells become the predominant subset throughout the body. Thus, in adults, especially the elderly population, the TCR diversity of naïve T cells that have the potential to recognize new antigens has been significantly reduced (compared with in childhood). It may happen that during many rounds of naïve T-cell patrol and circulation, a T-cell clone expressing a particular TCR that can recognize SARS-CoV-2 cannot be selected. If the immune system is unable to correctly identify a new antigen and activate the adaptive immune response, only innate immunity is activated to clear the pathogens, and the balance between viral reproduction and the innate immune response may be disrupted. If the immune system continues to fail to produce a specific adaptive immune response that can recognize SARS-CoV-2 over a long period, it is inevitable that the virus will attack all susceptible tissues and organs."
PS: In essence the quantity of Naïve T cells are age dependent and they present a major impact on the ability to identify new antigens. So,rather than an "immune overreaction problem," the immune system in patients with severe instances may have a "pathogen identification problem" - and this could be why children exhibit minimal symptoms and a low mortality rate. Thus Increasing the number of naïve T cells or the diversity of TCRs may be a feasible technique to improve the host's ability to "search for and eliminate" developing lethal infections that have never been seen by the immune system.
Now, a Chinese team of researchers from Sichuan University, hypothesize that Naïve T cells may contribute to lower mortality rates observed. Their explanation as below.
"Naïve T cells retain their specificity by expressing unique T-cell receptors (TCRs) but remain uncommitted to their helper fate until they encounter antigens presented by antigen-presenting cells (APCs). Each naïve T cell moves through the blood to the lymph nodes every 12–24 h, but only 1 in 10 naïve T cells may respond to any given antigen. If naïve T cells do not bind to any APC-presented MHC/antigen complexes, they exit through the thoracic duct and travel back into the blood. Once a naïve T cell encounters the corresponding MHC/antigen complex, it stops circulating, becomes activated, and proliferates and differentiates into effector and memory T cells with identical antigen specificity.
Thus, the number of naïve T cells may be key to assisting the body in identifying and coping with SARS-CoV-2 infections. For everyone, both young and old, this virus is a new pathogen that has never been encountered by their immune system. Therefore, in children's immune systems, there is essentially no difference between SARS-CoV-2 and common pediatric pathogens such as respiratory viruses, enteroviruses, and conditioned pathogenic bacteria. The immune system needs only to recognize it, activate the adaptive immunity, and store the memory T cells, which is not different from the way in which these cells cope with other pathogens. For example, when a child first enters kindergarten, close contact with other children exposes the child to a large number of new pathogens in a short period of time, which may cause the child to be continuously infected by various bacteria or viruses. This process usually lasts for several months, and in some cases, it even lasts for one or two years. Thus, in children, SARS-CoV-2 may not be substantially different from other newly encountered pathogens.
However, after childhood, the number of naïve T cells is significantly reduced, and memory T cells become the predominant subset throughout the body. Thus, in adults, especially the elderly population, the TCR diversity of naïve T cells that have the potential to recognize new antigens has been significantly reduced (compared with in childhood). It may happen that during many rounds of naïve T-cell patrol and circulation, a T-cell clone expressing a particular TCR that can recognize SARS-CoV-2 cannot be selected. If the immune system is unable to correctly identify a new antigen and activate the adaptive immune response, only innate immunity is activated to clear the pathogens, and the balance between viral reproduction and the innate immune response may be disrupted. If the immune system continues to fail to produce a specific adaptive immune response that can recognize SARS-CoV-2 over a long period, it is inevitable that the virus will attack all susceptible tissues and organs."
PS: In essence the quantity of Naïve T cells are age dependent and they present a major impact on the ability to identify new antigens. So,rather than an "immune overreaction problem," the immune system in patients with severe instances may have a "pathogen identification problem" - and this could be why children exhibit minimal symptoms and a low mortality rate. Thus Increasing the number of naïve T cells or the diversity of TCRs may be a feasible technique to improve the host's ability to "search for and eliminate" developing lethal infections that have never been seen by the immune system.
