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Protective immunity of BALB/c mice immunized with simian virus 40 (SV40) large T antigen (TAg) against SV40-transformed, TAg-expressing mKSA tumor cells is critically dependent on both CD8؉ and CD4 ؉ T lymphocytes. By depleting mice of T-cell subsets at different times before and after tumor challenge, we found that at all times, CD4 ؉ and CD8 ؉ cells both were equally important in establishing and maintaining a protective immune response. CD4؉ cells do not contribute to tumor eradication by directly lysing mKSA cells. However, CD4؉ lymphocytes provide help to CD8 ؉ cells to proliferate and to mature into fully active cytotoxic T lymphocytes (CTL). Depletion of CD4؉ cells by a single injection of CD4-specific monoclonal antibody at any time from directly before injection of the vaccinating antigen to up to 7 days after tumor challenge inhibited the generation of cytolytic CD8 ؉ lymphocytes. T helper cells in this system secrete the typical Th-1 cytokines interleukin 2 (IL-2) and gamma interferon. Because in this system TAg-specific CD8؉ cells secrete only minute amounts of IL-2, it appears that T helper cells provide these cytokines for CD8 ؉ T cells. Moreover, this helper effect of CD4 ؉ T cells in mKSA tumor rejection in BALB/c mice does not simply improve the activity of TAg-specific CD8 ؉ CTL but actually enables them to mature into cytolytic effector cells. Beyond this activity, the presence of T helper cells is necessary even in the late phase of tumor cell rejection in order to maintain protective immunity. However, despite the support of CD4 ؉ T helper cells, the tumor-specific CTL response is so weak that only at the site of tumor cell inoculation and not in the spleen or in the regional lymph nodes can TAg-specific CTL be detected.

Abstract. Recycling of 46,000 Mr mannose 6-phosphate receptor (MPR 46) was investigated by microinjection of Fab fragments against small epitopes within the cytoplasmic domain of the receptor. Fab fragments against the peptide 43-47 (Ala-Tyr-Arg-Gly-Val) efticiently blocked return of MPR 46 to the TGN. Antibody-induced redistribution resulted in accumulation of MPR 46 within an endosomal compartment, from which it recycled to the plasma membrane. Rab5 and rab7, markers for early and late endosomes, respectively, were not detectable in the compartment of redistributed MPR 46, suggesting that it represents a specialized endosomal subcompartment. The bulk of redistributed MPR 46 did not colocalize with endocy-

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