Reticuloendotheliosis virus REV-T(REV-A)-induced neoplasia: development of tumors within the T-lymphoid and myeloid lineages

Abstract

Infection of 1-day-old chicks with reticuloendotheliosis virus strain T induces a neoplastic disease that kills the chicks 7 to 14 days postinfection. In association with reticuloendotheliosis-associated virus (REV-A), reticuloendotheliosis virus T (REV-T) induces tumors that are predominantly immunoglobulin M (IgM) negative. We examined a variety of REV-T(REV-A)-induced tumors and tumor-derived cell lines and concluded that the principal IgM-negative tumors that develop in REV-T(REV-A)-infected chicks are neither pre-B or pre-B-pre-T but rather mature T lymphoid and myeloid. Without exception, the immunoglobulin heavy- and light-chain loci were in germ line configuration. Furthermore, the cell lines expressed neither sterile transcripts of the heavy- or light-chain immunoglobulin genes nor elevated levels of c-myb, two characteristics associated with murine pre-B lymphomas. Cell lines were also examined by using monoclonal antibodies for expression of a variety of cell surface markers expressed on B lymphocytes and/or T lymphocytes and/or myeloid cells. These reagents defined two types of IgM-negative tumor cell lines, one CIa+ CT-3+ (T lymphoid) and the other CIa+ CT-3-. By using the same approaches, tumor development was examined following REV-T(REV-A) infection at 1 and 3 weeks post-hatching of cyclophosphamide-treated chicks shown to be devoid of B-lymphoid cells. Again, the tumors that developed were either CIa+ CT-3+ (T lymphoid) or CIa+ CT-3-. Furthermore, the frequency and rate with which IgM-negative tumors developed in cyclophosphamide-treated chicks were not different from those observed in normal chicks. In 3-week-old cyclophosphamide-treated chicks, the presence of CIa+ CT-3- tumors bearing hematopoietic lineage markers, such as CLA-3 and 5M19, are most likely to have been derived from cells within the myeloid lineage.