CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus–transformed B cells

Abstract

Epstein-Barr virus (EBV)-

Virus-Specific Cytotoxic CD4+ T Cells for the Treatment of EBV-Related Tumors

“…However, a small fraction of these cells has entered the lytic cycle and therefore could be successfully targeted by a lytic Ag-specific T cells. Although we cannot completely exclude the presence of a reactivity to B cell-associated Ags, as recently advanced by Long et al (34), nonetheless the CD4 + T cells they generated were stimulated using the mini-LCL instead of the LCL; this excludes the reactivation of lytic cycle-specific T cells and potentially strongly skews toward (thus overestimating) the selection of autoantigen-specific T cells. In contrast, the matter of specificity is somehow of academic interest because the infusion of CTLs containing a large proportion of CD4 + T cells of undefined specificity was carried out in patients without adverse events, thus indicating that such B cell-specific T cells, if present, likely target an Ag(s) overexpressed by tumor cells (5).…”

“…2A), suggested a preferential recognition of viral Ags associated with the lytic cycle. Nonetheless, the remaining minimal recognition of mini-LCL does not allow to completely exclude the presence of a reactivity against latent Ags or putative B cell-associated Ags (34). Interestingly, the reduced cytotoxicity in mini-LCL compared with LCL was not due to an intrinsic lower susceptibility to lysis of mini-LCL, as both LCL and mini-LCL were equally lysed by alloreactive T cell cultures (Supplemental Fig.…”

T-Cell Responses to EBV

“…CD4+ T cells incapable of direct recognition of EBV-positive cells could still be of value, however, by providing T-cell help to the overall immune response. Cultures of T cells prepared using LCLs as stimulators also include CD4+ T cells specific for non-viral antigens upregulated in B cells by EBV transformation Long et al 2009). These cellular-antigen-specific CD4+ T cells can also control LCL outgrowth and may therefore enhance the anti-tumour effect, but do not appear to be essential since T-cell lines prepared without the use of LCLs, presumably lacking such responses, yield clinical responses in transplant recipients with PTLD or undergoing EBV reactivation (Gerdemann et al 2012;Icheva et al 2013).…”

Immune defence against EBV and EBV-associated disease

“…While this may reflect the importance of CD4 help in adoptively transferred preparations, CD4+ T cells may also be acting as effectors in their own right. Thus LCL-stimulated preparations have been shown to contain cytotoxic CD4+ T cells capable of LCL recognition and specific either for EBV latent and lytic proteins [6, 49,50] or for cellular antigens whose expression is up-regulated by EBV infection [51].…”