CLONED HUMAN CD8(-LYMPHOCYTES PROTECT HUMAN PERIPHERAL-BLOOD LEUKOCYTE-SEVERE COMBINED IMMUNODEFICIENT MICE FROM HIV-1 INFECTION BY AN HLA-UNRESTRICTED MECHANISM() CYTOTOXIC T)

The ability to infect human peripheral blood leukocyte-reconstituted s evere combined immunodeficient (hu-PBL-SCID) mice with HIV has allowed evaluation of several strategies for preventing or treating infection . In one study, hu-PBL-SCID mice derived from HIV gp160-vaccinated don ors were shown to resist HIV infection, and resistance correlated best with in vitro assays of cellular immunity. We have assessed directly the importance of cellular immunity to HIV in the present experiments by the adoptive transfer of HLA-A3-restricted HIV-1 Nef-specific or HL A-B14-restricted Gag-specific CD8(+) CTL clones to SCID mice bearing H LA-matched or mismatched PBL grafts. Multiple inoculations of CTL befo re and after HIV-1 exposure protected HLA-matched hu-PBL-SCID mice fro m infection, but initiation of CTL therapy on the same day as HIV infe ction was much less effective. However, at the high numbers of CTL req uired for complete protection from HIV infection, many HLA-mismatched hu-PBL-SCID mice were also protected by pre-exposure CTL transfer. Tra nsfer of CTL with a different specificity (HTLV-1 Tax) to HLA-matched hu-PBL-SCID mice also afforded partial protection. These results sugge st that HLA-restricted cytotoxicity may be less important than other n onspecific effector mechanisms for the inhibition of HIV-1 infection i n vivo.