Essential role for T cells in human B-cell lymphoproliferative disease development in severe combined immunodeficient mice

Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease (BLPD) -like lesions develop in severe combined immunodeficient (SCID) mice inocul ated with peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors, We used this model to investigate the pathogenesis of EBV-associate d BLPD. Tumour incidence fell from 81% to 11% when only B cells were inocul ated, suggesting a key role for T cells in tumour formation. This was furth er underlined by the reduction in tumour incidence from 76% to 7% when PBMC s 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 transcript ase-polymerase chain reaction (RT-PCR) expressed mRNA for interleukin (IL) 2, 4, 6, 10 and interferon (IFN) gamma. This is the cytokine pattern seen i n activated T cells and includes B-cell growth factors. III situ hybridizat ion studies confirmed that the tumour cells themselves express the growth f actors. which is consistent with autocrine-stimulated tumour growth. Our results suggest the following sequence of events: (1) T cells are essen tial for the initial outgrowth of tumorigenic EBV +ve B cells in vivo; (2) the neoplasm sustains its growth in an autocrine, cytokine-stimulated manne r; and (3) established tumours become independent of T-cell help.