Screening of viral specific T-cell lines for HLA alloreactivity prior to adoptive immunotherapy may prevent GvHD

Abstract

Immune deficiency and subsequent viral infection or reactivation is a common problem, particularly after stem cell transplantation. Virus specific T-cell adoptive immunotherapy across HLA barriers is increasingly being utilized as a treatment modality in immunocompromised patients. However, it was recently shown that nearly all viral specific memory T-cells are also allo-HLA reactive [1]. At least 45% of virus specific T-cell clones and most T-cell lines were shown to specifically crossreact against allogeneic HLA molecules. The allogeneic crossreactivity of CD8 and CD4 T-cells is directed primarily against HLA class I and II respectively [1–7], however, 3 viral specific CD8 T-cell clones have also been reported to exhibit allogeneic HLA class II crossreactivity [1,8]. As a consequence CD8 and CD4 T-cell adoptive immunotherapy across HLA barriers may be complicated by graft vs host disease (GvHD).