EBV INDUCES PROLIFERATION OF IMMATURE HUMAN THYMOCYTES IN AN IL-2-MEDIATED RESPONSE

The receptor for EBV, CD21, is expressed on a population of immature h uman thymocytes and facilitates infection of these cells by EBV, Thymo cytes infected by EBV become responsive to exogenous rIL-2- or CD2-med iated stimulation in vitro., To address whether such costimulation may be provided by thymic presenting cells and to study the cellular effe cts of EBV infection, the present work utilizes thymocyte cultures con taining autologous thymic presenting cells, In the presence of these p resenting cells, EBV induces proliferation of thymocytes, EBV infectio n promotes the formation of adhesions between two populations of cells in an APC responder fashion, and separation of these two populations abrogates the proliferative response to EBV, The response is mediated by IL-2 because Ab blocking of the IL-2R inhibits proliferation as doe s cyclosporin A, EBV promotes an expansion in the number of CD4(+)8(+) thymocytes, and the proliferating population is vulnerable to TCR/CD3 -generated signals, indicating that the responding cells are phenotypi cally and functionally immature, Finally, addition of exogenous IL-2 t o EBV-exposed thymocytes promotes a second wave of proliferation, Phen otypic characterization of the EBV-induced, IL-2-responding cells show s them to express reduced levels of CD1 and a transitional CD4(high)8( low) phenotype, These data characterize the cellular response to EBV i nfection in thymocytes and may offer insight into EBV-associated T lin eage malignancies and autoimmune disorders.