C3H/HeN mice were inoculated i.p. with viable vaccinia virus to generate virus-reactive helper T cell activity. 850R X-irradiated spleen cells from vaccinia virus-primed or unprimed mice as helper cells were stimulated in vitro with either trinitrophenyl (TNP)-modified syngeneic spleen cells (TNP-self), vaccinia virus-infected spleen cells (virus-self), or cells modified with TNP subsequent to virus infection (virus-self-TNP) in the presence of normal C3H/HeN spleen cells (responding cells). After 5 days of culture, effector cells were tested for anti-TNP delayed-type hypersensitivity (DTH) responses by adoptive transfer into footpads of syngeneic C3H/HeN recipient mice together with TNP-self. The results demonstrate that spleen cells from virus-primed mice failed to enhance anti-TNP DTH responses when in vitro stimulation was provided by either virus-self or TNP-self alone. In contrast, spleen cells from vaccinia virus-primed mice, but not from unprimed mice, could augment anti-TNP DTH responses when stimulated by virus-self-TNP. Such a helper activity provided by vaccinia virus-primed mice was shown to be antigen-specific, and mediated by Lyt-1+2-T cells. DTH effector cells enhanced by helper cells were also antigen-specific and Lyt-1+2-T cells. Furthermore, vaccinia virus-reactive helper T cell activity could be applied to augmented induction of anti-tumor DTH responses by stimulation with virus-infected syngeneic fibrosarcoma tumor cells. Thus, these results provide evidence for the role of antigen-specific helper T cells in augmenting the development of DTH responses to cell surface antigens including tumor antigens.
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