IL-2 Regulates Perforin and Granzyme Gene Expression in CD8+ T Cells Independently of Its Effects on Survival and Proliferation
I know this doesn't sound exciting to you, but it does to me. See I am slowly piecing the puzzle together that made my Sequential Cancer Treatment work so far.If I knew how complex the biochemistry of our immune system was, I would asked for cliff notes.
"Granule-mediated cytotoxicity is one of the major mechanisms used by CD8+ T cells to eliminate harmful or foreign bodies, such as virus-infected cells, tumors, and allografts. After Ag recognition, activated CD8+ T cells release the contents of their cytotoxic granules into the extracellular space, where they are taken up by the target cell, and apoptosis is initiated (1). The cytotoxic granules contain a number of molecules, including the pore-forming protein, perforin, and serine proteases, known as granzymes. Perforin was originally thought to cause cell lysis by penetrating the target cell membrane (2), but recent work favors the theory that perforin functions by enabling the granzymes to escape from endosomes into the cytosol of the target cell (3, 4). Whatever its exact role, perforin is essential, because Ag-specific granule-mediated cytotoxicity is absent in perforin-deficient CD8+ T cells and NK cells (5)."
I think I can do some hand waving but I still need to know how my immune system was able to differentiate between self (the body) and non-self (the tumor). I believe one of the keys may be the T-reg cells.
"These studies suggest that IL-2 itself may either directly or indirectly play an important role in the development and/or function of this unique population of CD25+ suppressor cells."
Source:http://jem.rupress.org/cgi/content/full/188/2/287
CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production By Angela M. Thornton and Ethan M. Shevach
"Regulatory T cells (sometimes known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. The existence of a dedicated population of suppressive T cells was the subject of significant controversy among immunologists for many years. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their critical role in the vertebrate immune system. Interest in regulatory T cells has been heightened by evidence from experimental mouse models demonstrating that the immunosuppressive potential of these cells can be harnessed therapeutically to treat autoimmune diseases and facilitate transplantation tolerance or specifically eliminated to potentiate cancer immunotherapy.
T regulatory cell populations
T regulatory cells are a component of the immune system that suppress immune responses of other cells. This is an important "self-check" built into the immune system so that responses do not go haywire. Regulatory T cells come in many forms, including those that express the CD8 transmembrane glycoprotein (CD8+ T cells), those that express CD4, CD25 and Foxp3 (CD4+CD25+ regulatory T cells or "Tregs") and other T cell types that have suppressive function. These cells are involved in closing down immune responses after they have successfully tackled invading organisms, and also in keeping in check immune responses that may potentially attack one's own tissues (autoimmunity).
CD4+Foxp3+ regulatory T cells have been referred to as "naturally-occurring" regulatory T cells to distinguish them from "suppressor" T cell populations that are generated in vitro. The regulatory T cell field is further complicated by reports of additional suppressive T cell populations, including Tr1, CD8+CD28-, and Qa-1 restricted T cells. However the contribution of these populations to self-tolerance and immune homeostasis is less well defined."
Source:Wikipedia
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