In the human immune response, an encounter with a pathogen results in the rapid division of immune cells which neutralize and kill viruses, bacteria and parasites. While this rapid increase in the number of immune cells in the body is necessary for a robust and effective immune response, once the pathogen has been cleared it is essential that immune cell levels be brought back down to normal. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), are one type of immune cell that follows this pattern of expansion and contraction. In the presence of an antigen, CD8+ T cells specific for that antigen divide rapidly, seeking out and killing infected cells and pathogens. When the threat has been cleared, high levels of CD8+ T cells specific for a single antigen are no longer necessary, and the majority of CD8+ T cells die by apoptosis. The surviving CD8+ T cells differentiate into memory T cells, allowing the body to respond more quickly and effectively the next time it encounters the same antigen. This process is essential for maintaining immunity to diseases; the memory T cells and B cells produced after an initial exposure are the reason that, for example, you only get chicken pox once. Similarly, memory T cells and B cells enable the body to prevent infection by pathogens against which it has been vaccinated.
In a paper published in the Journal of Immunology just this week, Soderquest, et al. examine the relationship between CD8+ s and natural killer cells (NK cells) after an infection has been cleared. NK cells are an important part of innate immunity – that is, the rapid and general immune response that includes both physical barriers to infection (i.e. the skin and mucosa) and non-specific killing cells like the NK cell. During the innate immune response, NK cells identify and kill cells that are either infected with viruses or are tumorigenic. Apart from their role in the innate immune response, recent studies have shown that NK cells play an important part in the development of the more specific adaptive immune response, particularly in promoting the differentiation of CD4+ “helper” T cells (Th cells). In investigating the relationship between CD8+ T cells and NK cells, Soderquest et al. focused on the NKG2D pathway of NK cell killing. NKG2D is a protein expressed on the surface of NK cells that binds to NKG2D ligand (NKG2DL) on a target cell and induces apoptosis via the perforin/granzyme pathway. The authors of this article hypothesized that NK cells influence the development of CD8+ T cell-mediated adaptive immunity by killing activated CD8+ T cells via the NKG2D/perforin pathway.
