vitro when human B cells are infected with EBV in the absence of T cells. 
The cells have a immunoblastoid or plasmacytoid appearance and are usually 
CD19, CD20, CD21 and CD24 positive (12,16,17). Like Burkitt lymphoma 
cells, the lymphoblasts express EBV nuclear antigen 1 (EBNA1) but unlike 
Burkitt lymphoma cells they express all of the five other virus encoded latent 
cycle nuclear antigens and are positive for most latent membrane proteins. In 
addition they express a number of cell adhesion molecules. All these 
phenotypic features would make them intensely vulnerable to cytotoxic T cell 
killing in a normal individual and it is only the profound suppression of the 
immune system after transplantation which permits their outgrowth. The B 
cell proliferation is polyclonal in the early stages but eventually becomes 
oligoclonal or monoclonal. 
Early in the illness fever and malaise are present. The proliferating 
lymphoblasts may then produce a number of disease patterns. They may 
diffusely infiltrate a number of organs including lung, liver, kidney, gut, bone 
marrow and central nervous system. Alternatively a classic lymphoma pattern 
is seen with lymphadenopathy, hepatosplenomegaly, and a biopsy appearance 
of immunoblastic lymphoma. Rarely a predominantly leukemic picture occurs. 
Initial reactivation of EBV associated with an infectious mononucleosis like 
illness may resolve. But once frank lymphproliferation has occurred, the 
course is usually rapidly progressive. 
As yet there is no effective treatment for EBV lymphoproliferative disorders. 
Withdrawal of immunosuppression which is effective in around 50% of the 
cases which follow transplantation of solid organs is rarely effective post BMT. 
Acyclovir may disrupt the replicative lytic cycle of the linear virus and 
interferon may prevent infection of fresh lymphocytes, but neither approach 
can significantly modify the growth of already transformed B cells which 
contain non replicating (circular virus). Recent reports suggest that infusions 
of monoclonal antibodies to CD21 and CD24 may eradicate infected B 
lymphoblasts in some patients with oligoclonal proliferations (18) but no 
effective treatment is available for monoclonal disease. 
3.5 Importance of the Immune System in EBV Control 
A number of lines of evidence suggest that EBV specific CD8+ CTL are the 
most important defense mechanism against outgrowth of EBV infected B 
cells. These cells recognize peptide fragments derived from viral antigens 
expressed on the surface of B cells in association with MHC. Studies using 
EBV latent proteins expressed in vaccinia virus constructs have shown that a 
number of antigens can serve as targets (19,20). 
The importance of cytotoxic T cells is illustrated by patients with the rare 
familial disorder X-linked lymphoproliferative syndrome. These patients have 
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