Activation, Differentiation, and Migration of Naive Virus-Specific CD8 super(+) T Cells during Pulmonary Influenza Virus Infection

The low precursor frequency of individual virus-specific CD8 super(+) T cells in a naive host makes the early events of CD8 super(+) T cell activation, proliferation, and differentiation in response to viral infection a challenge to identify. We have therefore examined the response of naive CD8 super(+) T cells to pulmonary influenza virus infection with a murine adoptive transfer model using hemagglutinin-specific TCR transgenic CD8 super(+) T cells. Initial activation of CD8 super(+) T cells occurs during the first 3 days postinfection exclusively within the draining lymph nodes. Acquisition of CTL effector functions, including effector cytokine and granule-associated protease expression, occurs in the draining lymph nodes and differentially correlates with cell division. Division of activated CD8 super(+) T cells within the draining lymph nodes occurs in an asynchronous manner between days 3 and 4 postinfection. Despite the presence of Ag for several days within the draining lymph nodes, dividing T cells do not appear to maintain contact with residual Ag. After multiple cell divisions, CD8 super(+) T cells exit the draining lymph nodes and migrate to the infected lung. Activated CD8 super(+) T cells also disseminate throughout lymphoid tissue including the spleen and distal lymph nodes following their emigration from draining lymph nodes. These results demonstrate an important role for draining lymph nodes in orchestrating T cell responses during a local infection of a discrete organ to generate effector CD8 super(+) T cells capable of responding to infection and seeding peripheral lymphoid tissues.