Tamara Reshef

Vaccination against experimental autoimmune encephalomyelitis using a subencephalitogenic dose of autoimmune effector T cells. (2) Induction of a protective anti-idiotypic response

We previously reported that a subencephalitogenic dose (10(4) of activated anti-BP Z1a T cells rendered Lewis rats significantly resistant to EAE induced either actively or adoptively. This resistance was specific to EAE and persisted for over 4 months. The experiments reported in this paper were done to investigate the mechanisms of this resistance. We found that the state of vaccination was marked by a decrease in the in vitro proliferation and in vivo DTH responses to BP. Resistance could be transferred to recipient rats with the thymus or spleen cells of donor vaccinated rats. Vaccination led to the appearance of proliferative and DTH responses that were specifically directed to the Z1a T cells. The kinetics and compartmentalization of this anti-idiotypic responsiveness was studied by vaccinating rats in the hind footpads and monitoring the proliferative reactivity of the draining popliteal lymph node (PLN) and distal cervical lymph node (CLN) cells at various times. We found that the anti-idiotypic reactivity was confined to the PLN on days 5-6 and thereafter became systemic. Excision of the PLN on day 6, but not on days 3 or 11, robbed the rats of their acquired resistance to EAE. In contrast, the PLN cells of the vaccinated rats transferred resistance to naive donors. Thus, the lymphoid population containing cell-mediated anti-idiotypic responsiveness served as a vehicle of resistance. These results suggest that anti-idiotypic T-cell immunity to autoimmune effector T cells is involved in the resistance to EAE induced by T-cell vaccination.

Vaccination against experimental autoimmune encephalomyelitis using a subencephalitogenic dose of autoimmune effector cells (1) characteristics of vaccination

We previously reported that rats could be vaccinated against EAE by inoculation with 10(7) anti-basic protein (anti-BP)-activated T cells raised as long-term lines. The activated T lines were irradiated (1,500 rads) to prevent them from causing EAE. We now report that a single inoculation of 10(4) or fewer cells of an activated anti-BP T-cell line did not cause clinical EAE but rather induced marked resistance to EAE produced by adoptive transfer of the anti-BP T cells. Resistance was less effective against EAE induced by active immunization to BP. Vaccination was immunologically specific, long lasting, and could be effected by various routes of administration.

Non-thymic malignant lymphomas induced in C57BL/6 mice by cloned dualtropic viruses isolated from hematopoietic stromal cell lines☆

Abstract Retroviruses cultivated from adherent bone marrow cells of C57BL/6 mice have been cloned in vitro and were shown to be potent inducers of reticulum cell neoplasms (RCN) (a non-thymic malignant lymphoma) in C57BL/6 mice. The RCN-inducing isolates were high-titer dualtropic viruses and presumably were recombinant in the major envelope glycoprotein gp 70 . The virus clones constituted part of a larger group of equally high titer dualtropic isolates most of which were innocuous in vivo . Previously, we have shown that thymic malignant lymphomas were induced by other, thymotropic viruses isolated from C57BL/6 mice, viruses that were shown to be recombinant in gp 70 . Thus, non-thymic malignant lymphomas were induced in C57BL/6 mice by specific dualtropic isolates, whereas thymic malignant lymphomas were caused by other, distinctive recombinant viruses.

Involvement of peritoneal macrophages and spleen stromal cells in X-irradiation-induced reticulum cell neoplasms in C57BL/6 mice☆

Some correlation was observed between the occurrence of FA-positive PE-MO and spleen stromal cells (removed from X-irradiated RCN-bearing old-adult B6 mice) and the generation of RCN. No significant correlation was found between the viral content of lymphoid organs from the same mice and the occurrence of RCN. The main viral particle detected in lymphoid organs from radiation-induced RCN-bearing mice was the xenotropic virus. Ecotropic viruses were detected in a few spleens and Payer patches from such mice. These ecotropic viruses showed very poor lymphomagenic activity and required 400R X-ray as a cofactor. No dualtropic viruses were detected. However, inoculation of ecotropic (SFA2) helper virus to X-irradiated old-adult B6 mice, resulted in an efficient rescue of lymphomagenic viruses, enriched with phenotypically mixed, dualtropic viruses. Some of these DT viral preparations were cloned and seemed to consist mainly of xenotropic sequences. Thus, inoculation of helper viruses influenced the generation and selection of DT viruses. Such viral preparations, enriched with DT viruses, had a better lymphomagenic activity compared to endogenous ecotropic viruses, isolated from radiation-induced RCN-bearing mice. Indirect evidence suggested the involvement of a defective (xenotropic and possibly adjacent cellular genes) particle in lymphoma induction. To conclude, a possible mechanism for the development of radiation-induced RCN is suggested, emphasizing the role of MO in such a process.