Epstein–Barr virus (EBV)‐positive B‐cell lymphoproliferative disease (BLPD)‐like lesions develop in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMCs) from EBV‐seropositive donors. We used this model to investigate the pathogenesis of EBV‐associated BLPD. Tumour incidence fell from 81% to 11% when only B cells were inoculated, suggesting a key role for T cells in tumour formation. This was further underlined by the reduction in tumour incidence from 76% to 7% when PBMCs were depleted of CD4 positive (+ve) helper T cells. Tumour outgrowth was also reduced when PBMC were depleted of CD8 +ve, CD45RA +ve or CD45RO +ve T cells. The majority of PBMC‐derived tumours analysed by reverse transcriptase–polymerase chain reaction (RT–PCR) expressed mRNA for interleukin (IL) 2, 4, 6, 10 and interferon (IFN) γ. This is the cytokine pattern seen in activated T cells and includes B‐cell growth factors. In situ hybridization studies confirmed that the tumour cells themselves express the growth factors, which is consistent with autocrine‐stimulated tumour growth.

Our results suggest the following sequence of events: (1) T cells are essential for the initial outgrowth of tumorigenic EBV +ve B cells in vivo; (2) the neoplasm sustains its growth in an autocrine, cytokine‐stimulated manner; and (3) established tumours become independent of T‐cell help.