Transplantation of CD4+ T cell clones into SCID mice

Engraftment of congenic (BALB/c) or semi-syngeneic (dm2) CD4+ T cell clones into immunodeficient SCID mice was investigated in two experimental systems: the adoptive transfer of Iad-restricted, anti-host-reactive ('self-reactive') CD4+ T cell clones, and the adoptive transfer of OVA-specific CD4+ T cell clones. SCID mice transplanted with 10(4)-10(5) purified BALB/c CD4+ T cells select anti-host-reactive T cells for engraftment. Anti-SCID-reactive T cell clones derived from such preselected CD4+ T cell populations could be successfully engrafted into secondary SCID recipients. In a second series of experiments, Iad-restricted, self-reactive BALB/c CD4+ T cell clones established in long-term culture from unselected, normal BALB/c spleen cell populations were transferred into SCID mice. Not a single clone from this panel could be transplanted into the immunodeficient host. Intravenous injection of OVA-primed dm2 (Ld-) CD4+ T cells into OVA-immunized young SCID (Ld+) mice repopulated the splenic and peritoneal T cell compartment of all transplanted mice. OVA-specific dm2 CD4+ T cells from the spleens of transplanted SCID mice were (sub)cloned under limiting dilution conditions in vitro. Only some of these clones repopulated OVA-immunized SCID recipients after retransplantation in vivo. Serial transfer experiments with a selected OVA-specific dm2 CD4+ T cell clone indicated that the route of cell transfer (i.p., but not i.v.), but not the route of OVA immunization of the host (i.v. or i.p.) were critical for successful engraftment of this clone. Hence, selected CD4+ T cell clones can be successfully engrafted into SCID mice if (i) the population from which clones are derived is preselected in SCID mice, (ii) the in vitro culture period of T cells is restricted to a few months, and (iii) alternative routes of cell transfer are tested. In infectious disease models, protective T cell clones can be identified in vivo using the described system. In addition, the importance of T cells with defined phenotype and effector functions in the pathogenesis of autoimmune disorders can be assessed in this system.