Resection of renal cell carcinomas with inferior vena caval extension using deep hypothermic circulatory arrest.

Renal cell carcinoma with tumour thrombus extension into the inferior vena cava presents a difficult surgical challenge. The conventional surgical approach, which involves isolating the inferior vena cava, incising its wall and removing the thrombus, can have high incidences of perioperative mortality and embolization of the tumour thrombus compounded by severe hemorrhage. Four patients with renal cell carcinomas extending into the inferior vena cava were supported with cardiopulmonary bypass and deep hypothermic circulatory arrest during tumour excision. All of the operations were successfully performed with no mortality and minimal morbidity. The technique allowed the surgeon to operate in a bloodless field, thereby improving visibility and allowing complete tumour excision without significantly prolonging operative time. It is believed that this technique has improved the safety and technical feasibility of what had previously been a complicated and risky surgical procedure.

Transfer of endogenous retroviral superantigen from donor to recipient B cells following priming to induce peripheral T cell tolerance.

Endogenous retroviral superantigens such as vSAG-7 are highly stimulatory for T cells through interaction with the T cell receptor on the basis of V beta usage. Priming of adult MMTV 7-negative mice with vSAG-7-expressing cells has been shown to result in peripheral V beta 6/CD4+ T cell activation followed by tolerance to further interaction with the superantigen. The goal of the current study was to examine the cells presenting vSAG-7 during this initial burst of in vivo T cell activation. Priming of MMTV 7-negative BALB/c (H-2d) mice with DBA/2 (H-2d, MMTV 7+) spleen cells resulted in a 5- to 12-fold increase in the number of B cells in the lymph nodes. These B cells expressed increased levels of I-A and I-E class II MHC determinants. Use of MMTV 7-negative CB.17 (H-2d, Ighb) mice as recipients of DBA/2 (Igha) cells indicated that the increased number of B cells was of host, rather than donor, origin. The number of donor-derived (IgM/B220+) B cells observed during the course of vSAG-7-reactive V beta 6/CD4+ T cell activation was very low. Proliferation of unprimed T cells from MMTV 7-negative mice was induced during coculture with B cells from the lymph nodes of vSAG-7-primed recipients and was blocked by anti-class II MHC antibodies, as well as by an anti-vSAG-7 antibody. Highly purified host B cells from vSAG-7-primed recipients specifically stimulated the blastogenesis of V beta 6/CD4+ T cells in vitro. Collectively, the results indicate that following priming to induce peripheral tolerance, vSAG-7 is transferred from donor cells to class II MHC determinants on recipient B cells and is presented to the T cell repertoire by the autologous B cells.

T cell activation is not a prerequisite for peripheral tolerance induction to Mls 1a.

T cell interaction with endogenous retroviral superantigens in vivo results in either deletion of the reactive T cells or their transition to a state of unresponsiveness. We show here that introducing cells expressing the endogenous superantigen Mls 1a into an Mls 1b environment results in the induction of an anergic state with little or no depletion of V beta 6/CD4+ T cell from the peripheral T cell repertoire. Removal of B cells from the priming innoculum abrogates the induction of tolerance, indicating that presentation of Mls 1a by B cells induced the tolerance observed. The tolerant T cells are unable to respond to either presentation of Mls 1a on spleen cells or cross-linking anti-T cell receptor antibody in vitro. Although large increases in the cell size and numbers of reactive T cells are observed 2-3 days after priming with Mls 1a-presenting cells, this activation is not a requirement for the induction of tolerance because irradiated Mls 1a-presenting cells retained the ability to induce tolerance without these changes in the reactive T cell population. Furthermore, providing host T cells with Mls 1a and a costimulatory signal, in the form of high levels of the B7 determinant on the donor cells, did not circumvent the induction of tolerance. Collectively, these results indicate that the transition to an anergic state following interaction with endogenous superantigen in vivo is not dependent upon the activation of the reactive T cells.