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Most individuals first encounter the herpes virus, Epstein-Barr virus (EBV) in early childhood or late adolescence [114]. For infants and children, this exposure is usually asymptomatic or manifests as a nonspecific upper respiratory infection. On the other hand, a primary infection in an adolescent or an adult causes infectious mononucleosis (IM), characterized by fever, pharyngitis, lymphadenopathy, and an atypical lymphocytosis in over 50% of cases [62]. Following initial infection, latent infection of the parotid and salivary glands persists for life. Latent salivary gland infection is periodically interrupted by lyric virus production, shedding of EBV in saliva, and occasional secondary viremias [50, 116]. EBV also establishes a latent infection in B lymphocytes. These EBV-transformed B cells express only a limited profile of EBV-encoded antigens and rarely produce lytic virus [223]. In EBV-seropositive individuals, small numbers of these latently infected B cells, which can spontaneously transform in vitro, can be detected in the bloodstream throughout life [201]. Several studies in the mid-1970s demonstrated that patients with IM developed specific cell-mediated immune responses against EBV [ 122, 151, 186, 198]. Analysis of the function of the EBV-specific T cells generated demonstrated that they could both lyse EBV-infected targets and, at low effector to target ratios, inhibit the growth of clonigenic EBV-transformed B cells [122, 151, 186, 198]. Subsequent analyses revealed that following IM, immunocompetent individuals generate and sustain high frequencies of circulating EBV-specific cytotoxic T cells [13, 92, 105]. On the other hand, patients with acquired or inherited deficiencies of T cell-mediated immunity were found to be at risk for severe or fatal EBV-induced infections as well as for the development of EBV-driven polyclonal or monoclonal B cell lymphoproliferations [77, 135,141,172, 227]. These findings led to the hypothesis that EBV-specific T cell-

Adoptive immunotherapy for Epstein-Barr virus-associated lymphoproliferative disorders complicating marrow allografts