In order to have a more comprehensive understanding of the immune response of CD4 and CD8 T cells in olive flounder, we examine the in vivo proliferation of CD4- and CD8-positive T cells in response to nervous necrosis virus (NNV), an infectious disease that causes abnormal behavior and visual dysfunction in marine and freshwater fish [29,30,31,32], and foreign antigens keyhole limpet hemocyanin (KLH) and lipopolysaccharide (LPS), which are considered to be T cell-dependent and -independent antigens, respectively, and capable of initiating an immune response [33,34,35,36]. Here, CD8A is linked to infectious disease.