increase of cxcl13 levels facilitated the recruitment of intrahepatic cxcr5+cd8+t cells and, these types of cells produced high levels of hbv-specific interferon (ifn)-γ and il-21, which can help to improve the control of chronic hbv infection. cytotoxic t cells have been implicated in the progression of arthritis. the main involvement of rheumatoid arthritis is its joint involvement, the synovial membrane is characterised by hyperplasia, increased vascularity and infiltrate of inflammatory cells, mainly cd4+ t lymphocytes, which are the main organiser of cell-mediated immune responses. in different studies, rheumatoid arthritis is strongly linked to major histocompatibility complex (mhc) class ii antigens. the only cells in the body that express mhc class ii antigens are constitutive antigen-presenting cells. this strongly suggests that rheumatoid arthritis is caused by unidentified arthritogenic antigens. the antigen could be any exogenous antigen, such as viral proteins, or an endogenous protein. recently, a number of possible endogenous antigens have been identified, for example, human cartilage glycoprotein 39, heavy chain binding protein and citrullinated protein. activated cd4+ t lymphocytes stimulate monocytes, macrophages and synovial fibroblasts to elaborate the cytokines interleukin-1, interleukin-6 and tumour necrosis factor alpha (tnfa), and to secrete metalloproteinases. the first three of which are key in driving inflammation in rheumatoid arthritis. these activated lymphocytes also stimulate b cells to produce immunoglobulins, including rheumatoid factor. their pathogenic role is unknown, but may be due to complement activation through immune complex formation. moreover, several animal studies suggest that cytotoxic t cells may have a predominantly proinflammatory effect in the disease. it is also studied that the production of cytokines by the cd8+ cells may accelerate the progresses of the arthritis disease. cd8+ t cells have been found to play a role in hiv infection. hiv over time has developed many strategies to evade the host cell immune system. for example, hiv has adopted very high mutation rates to allow them to escape recognition by cd8+ t cells. they are also able to down-regulate expression of surface mhc class i proteins of cells that they infect, in order to further evade destruction by cd8+ t cells. if cd8+ t cells cannot find, recognize and bind to infected cells, the virus will not be destroyed and will continue to grow. furthermore, cd8+ t cells may be involved in type 1 diabetes. studies in a diabetic mouse model showed that cd4+ cells are responsible for the massive infiltration of mononuclear leukocytes into pancreatic islets. however, cd8+ cells have been shown to play an effector role, responsible for the ultimate destruction of islet beta cells. however, in studies with nod mice carrying a null mutation at the beta 2-microglobulin (beta 2-mu) locus and thus lacking major histocompatibility complex class i molecules and cd8+ t cells, it was found that they did not develop diabetes. cd8+ t cells may be necessary to resolve chemotherapy-induced peripheral neuropathy (cipn). mice without cd8+ t cells show prolonged cipn compared to normal mice and injection of educated cd8+ t cells resolve or prevent cipn. cytotoxic t-lymphocytes have been implicated in the development of various diseases and disorders, for example in transplant rejection (cytotoxic t-lymphocytes attack the new organ after detecting it as foreign, due to hla variation between donor and recipient); in excessive cytokine production in severe sars-cov-2 infection (due to an exaggerated lymphocyte response, a large amount of pro-inflammatory cytokines are generated, damaging the subject); inflammatory and degenerative diseases of the central nervous system, such as multiple sclerosis (t cells become sensitised to certain proteins, such as myelin, attacking healthy cells and recruiting more immune cells, aggravating the disease).