Individual Tumors of Multifocal EB Virus-Induced Malignant Lymphomas in Tamarins Arise from Different B-Cell Clones

Abstract

Cotton-top tamarins were inoculated with sufficient Epstein-Barr virus to induce multiple tumors in each animal within 14 to 21 days. The tumors consisted of large-cell lymphomas that contained multiple copies of the Epstein-Barr virus genome and generated Epstein-Barr virus-carrying cell lines showing no detectable consistent chromosomal abnormality. Hybridization of tumor DNA with immunoglobulin gene probes revealed that each lymphoma was oligo- or monoclonal in origin and that individual tumors from the same animal arose from different B-cell clones. Thus the virus induced multiple transformation events in tamarins in vivo to cause malignant tumors resembling the Epstein-Barr virus-associated lymphomas of patients with organ transplants.

Prevention of Epstein-Barr (EB) Virus-induced Lymphoma in Cottontop Tamarins by Vaccination with the EB Virus Envelope Glycoprotein gp340 Incorporated into Immune-stimulating Complexes

“…Histological and molecular biological criteria have been used to demonstrate that these tumours are induced by EB virus, that they are monoclonal or oligoclonal (Cleary et al, 1985) and are large cell malignant lymphomas consisting of immunoblastic and follicular centre cell types (Dorfman et al, 1982).…”

“…2 and are compared with those obtained in four unvaccinated control animals that had received the same dose of EB virus from the same batch as that used to challenge the vaccinated animals. Tumour development occurred in the control animals in the characteristic way (Cleary et al, 1985) with multiple lesions appearing during the 3rd week following challenge. All four vaccinated animals remained free of significant palpable lesions although some transient lymph node enlargement was detected.…”

“…Two weeks after the third injection the four tamarins received a challenge dose of EB virus (Cleary et al, 1985). The development of tumours in the animals was assessed by physical examination.…”

“…No side effects have ever been observed in a variety of species at the dosage level of iscoms required for effective vaccination . A recent formal toxicological study of local reactions to Quil A and to an iscom measles (Cleary et al, 1985) (a) in control animals B41 (©), B57 (A), B24 (O) and B36 (z~) and (b) in animals R69 (4k), Y20 (O), Y9 ('k) and RT0 (z~ vaccinated with gp340 iscoms. The tumour index is defined as the sum of the radii of palpable tumours in mm in an animal at the time indicated following virus challenge.…”

Virus-specific cytotoxic T cell responses are associated with immunity of the cottontop tamarin to Epstein–Barr virus (EBV)

“…Cottontop tamarins challenged with a large dose of EBV develop multiple B cell lymphomas within 14-21 days that contain the EBV genome [1]. In most cases the tumours are progressive and fatal, but a proportion of animals survive and in these individuals the tumours regress over a period of 8-12 weeks and these recovered tamarins are completely immune to a second virus challenge [1,2].…”