Delayed hypersensitivity in mice infected with reovirus. II. Induction of tolerance and suppressor T cells to viral specific gene products.

Abstract

We have found that route of inoculation and viral infectivity determine the ability of mice to generate immunocompetent T cells able to mediate in vivo delayed-type hypersensitivity (DTH) against reovirus. DTH reactivity is present when live virus is administered by the subcutaneous (s.c), i.p., i.v. routes and when ultraviolet (UV) inactivated virus is administered by the s.c. or i.p. routes. However, no DTH responses are elicited when UV-inactivated virus is administered by the i.v. route. The lack of DTH reactivity (tolerance) is due to active suppression and involves the generation of suppressor T cells, since 1) simultaneous administration of UV-inactivated virus by the i.v. route and live virus by the s.c. route prevents the induction of DTH reactivity, and 2) adoptive transfer experiments demonstrate that spleen cells from tolerant animals prevent the induction of DTH reactivity in animals immunized with live virus by the s.c. route. These suppressor cells are T cells, since their ability to suppress DTH reactivity is abrogated by treatment with anti-Thy 1.2 and C. Tolerance to reovirus as measured by DTH reactivity is serotype-specific. Using appropriate recombinant viral clones, it was demonstrated that serotype-specific tolerance and suppressor T cells are a property of the viral hemagglutinin, the viral protein that also determines serotype-specific humoral and cytolytic T cell responses.