The aim of the current study was to determine the ability of
antigen-driven cloned helper cell independent cytotoxic T lymphocytes (
HITc) to proliferate and to survive in vivo and to mediate
tumor therapy. The
HITc clone utilized (denoted 1.B6) was specifically cytolytic to FBL-3, a syngeneic Friend virus-induced murine
leukemia. Activation in vitro (48 hr) with FBL-3 induced secretion of
interleukin 2 (IL 2), expression of
IL 2 receptors (IL 2R), and in vitro proliferation. These cells could be "rested" for several weeks without stimulation, which resulted in reduced expression of IL 2R; however, restimulation with
antigen resulted in reinduction of IL 2R and proliferation. The ability of cloned
HITc to proliferate and to survive in vivo was examined in
cyclophosphamide (CY) pretreated donor mice congenic for the Thy-1 gene. Adoptively transferred cloned
HITc could be found in large numbers, and were widely distributed in vivo 1 wk after transfer. In
tumor therapy, 1.B6 cells when injected into a site of
tumor (i.p.) and used as an adjunct to CY were effective against disseminated FBL-3. In this circumstance, cloned 1.B6 cells could be recovered from cured mice 125 days after transfer and were shown to specifically lyse
tumor and proliferate in vitro in response to FBL-3. Thus as an adjunct to CY,
tumor-specific cloned
HITc are capable of eradicating disseminated
leukemia, persisting long-term in vivo, and providing specific immunologic memory.