Analysis of the T-cell micro-environment in Epstein-Barr virus-related post-transplantation B lymphoproliferative...

Epstein-Barr virus (EBV) post-transplantation B lymphoproliferative disease (BLPD) may undergo regression after immunosuppression withdrawal and restoration of EBV-specific cytotoxic T-cell (CTL) activity in the immunocompromised allografted host. The presence of morphologically normal T cells in the BLPD micro-environment may influence tumour behaviour in vivo. In this immunopathological study, the phenotype and the number of T cells and other immunoregulatory cells have been investigated in seven primary and four recurrent BLPD biopsies from nine solid organ transplant recipients. BLPD with either viral lymphadenopathic or polymorphic lymphoma appearances was found to contain sizeable T-cell populations, mainly of memory/helper (TCR alpha/beta +, CD3+, CD4+, CD45RO+) type. Cytotoxic (TCR alpha/beta +, CD3, CD8+, Tia-1+) T cells were strikingly low in all samples. Low CD28 and CD25 expression suggested that secondary signals for functional and sustained T-cell activation may be deficient in these tumours. No close correlation was found between the degree of T-cell infiltration and clinical outcome, although appreciably higher number of CD8+ T cells were detected in three BLPD tumours showing prolonged clinical remission after treatment. While some level of EBV-specific T-cell function may be present in untreated BLPD, the overall findings of this study suggest that the nature of T-cell infiltrates may reflect a response to immunosuppressive therapy rather than to EBV infection per se. The possibility that a local EBV-specific T-cell response is generated in BLPD undergoing regression after treatment needs to be investigated.