Regulation of tumor dormancy by cd4⁺ and cd8⁺ t cell subpopulations

The B cell lymphoma BCL₁ is a murine tumor, closely resembling human prolymphocytic leukemia, which regresses spontaneously after injection into BALB/c mice pre-immunized with the BCL₁ Ig. Although ∼ 10⁶ dormant BCL\ tumor cells are harbored in their spleens, 70% of these animals remain disease free for greater than 100 days following tumor transfer. Previous studies have demonstrated a role for antibody in inducing the dormant state; however, the mechanisms responsible for maintaining dormancy, and the alteration of those mechanisms leading to relapse, are yet to be elucidated. Experimentation in passively immunized SCID mice has demonstrated that adoptive transfer of Id-immune T cells increases the incidence and duration of the dormant state. We have further investigated the requirement of T cell subpopulations in maintaining dormancy by supplementing passively immunized SCID mice with enriched populations of Id-immune CD4, CD8 or both T cell populations prior to tumor challenge. This approach demonstrated a direct involvement of the CDS subpopulation in maintaining the dormant state, and suggested that CD4 cells enhanced the CDS cell effect by secreting IFN-7A second experimental approach was designed to test the requirement of T cell subpopulations in maintaining dormancy by depleting CD4, CDS or both populations with specific monoclonal antibodies in a panel of dormant mice. Collectively, these data indicated that the CDS subpopulation was responsible for modulating dormancy, and this activity was inhibited by neutralizing antibodies to IFN-γ.