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It is frequently assumed that this high efficiency of transformation is due to the absence of a primary immune response. However, cord blood lymphocytes stimulated with autologous LCL yield CD4<jats:sup>+<\/jats:sup>T cells that can completely inhibit the growth of LCL by a major histocompatibility complex-restricted cytotoxic mechanism mediated by granulysin and granzyme B. Because EBV-transformed B cells maintain the phenotype of antigen-activated B-cell blasts, they can potentially receive inhibitory or helper functions from CD4<jats:sup>+<\/jats:sup>T cells. To assess these functions, the effect of EBV-specific CD4<jats:sup>+<\/jats:sup>T cells on the efficiency of virus transformation of autologous B cells was assayed. Paradoxically, although the cytotoxic CD4<jats:sup>+<\/jats:sup>T-cell lines reduced EBV B-cell transformation at a high effector\/target ratio of 10:1, they caused a twofold increase in B-cell transformation at the lower effector\/target ratio of 1:1. Th1-polarized CD4<jats:sup>+<\/jats:sup>T cells were more effective at inhibiting B-cell transformation, but Th2-polarized cell lines had reduced cytotoxic activity, were unable to inhibit LCL growth, and caused a 10-fold increase in transformation efficiency. Tonsil lymphoid follicles lacked NK cells and CD8<jats:sup>+<\/jats:sup>T cells but contained CD4<jats:sup>+<\/jats:sup>T cells. We propose that CD4<jats:sup>+<\/jats:sup>T cells provide helper or cytotoxic functions to EBV-transformed B cells and that the balance of these functions within tonsil compartments is critical in establishing asymptomatic primary EBV infection and maintaining a stable lifelong latent infection.<\/jats:p>","DOI":"10.1128\/jvi.02608-06","type":"journal-article","created":{"date-parts":[[2007,2,22]],"date-time":"2007-02-22T01:26:06Z","timestamp":1172107566000},"page":"4766-4775","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Primary CD4<sup>+<\/sup>T-Cell Responses Provide both Helper and Cytotoxic Functions during Epstein-Barr Virus Infection and Transformation of Fetal Cord Blood B Cells"],"prefix":"10.1128","volume":"81","author":[{"given":"Georgina J.","family":"MacArthur","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, School of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Douglas","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Veterinary Pathology, Infection and Immunity, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Birchall","sequence":"additional","affiliation":[{"name":"Clinical Sciences at South Bristol"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, School of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.4.567"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00049-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200366597"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_3_2_6_2","first-page":"55","volume":"276","year":"2003","unstructured":"Bickham, K., and C. 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