Cellular immune response to viral infection: in vitro studies of lymphocytes from mice infected with Sindbis virus

The development and evanescence of cell-mediated immunity to Sindbis virus infection in the mouse was studied using in vitro lymphocyte transformation. Adult mice were inoculated subcutaneously with Sindbis virus, a group A arbovirus, and cells from the draining lymph nodes and spleen were examined temporally for their ability to incorporate ³H-Tdr in the presence of Sindbis virus antigen in vitro. Lymphocyte transformation was shown to be specific and dose-related. Better stimulation was obtained with live virus antigen than with inactivated virus antigen. Specific ³H-Tdr incorporation was markedly reduced when lymph node cells were pretreated with anti-θ and complement, but anti-mouse immunoglobulin also reduced the response. Specifically sensitized cells were present in the draining lymph nodes 3–4 days after primary Sindbis virus infection, peaked at 6 days, and returned to control levels by 16 days. The response in the spleen appeared later and disappeared later. Neutralizing antibody appeared by Day 4, rose rapidly, and plateaued at a high level. The secondary cellular response differed from the primary response by being somewhat earlier and being elicitable with an amount of inactivated virus antigen which was insufficient to produce a primary response.