The generation of cytotoxic reactivity in the spleens of adult male and female BALB/c mice infected with Coxsackievirus B-3 was compared. Cytotoxicity was measured by using an in vitro 51Cr release assay employing syngeneic virus-infected and uninfected fibroblasts as target cells. Males exhibited a stronger response and significant levels of cytotoxicity were evident by day 3 after infection. Generally activity detected at this time was not viral specific and both infected and uninfected target cells were lysed. Treatment of day 3 male spleen cells with anti-thy-1.2 + C abolished both reactivities indicating that each was mediated by cytotoxic T cells. Male cytotoxicity peaked on day 7 and effector cells obtained at this time were virus specific. In marked contrast, day 7 female immune cells caused little or no target cell lysis. Females, however, exhibited significant levels of cytotoxicity at earlier intervals, primarily between days 3 and 6. Although this activity then faded, a second wave of reactivity was observed in some between the 10th and 17th day. At all intervals female cytotoxicity was not viral specific and uninfected target cells were lysed as well or better than viral infected cells. Treatment of day 3 female spleen cells with anti-thy-1.2 serum + C significantly diminished cytotoxicity against infected targets but had no effect on activity directed against uninfected fibroblasts. The results indicate that the female response was composed of a mixture of different effector cell populations with T cells responsible for only a portion of the activity. These sex-related differences were specific for Coxsackievirus infection and were not observed in animals infected with vaccinia virus. The cytotoxic response of Coxsackievirus infected females was correlated with the finding that viral clearance was more rapid and early antibody production more vigorous than that observed in males.
This work was supported by National Institutes of Health Grants HL-17404 and T01-GM-00078 and by Grant-in-Aid 74-823 from the American Heart Association.