Herpes virus saimiri transformation of T cells in CD3γ immunodeficiency: phenotypic and functional characterization

Abstract

The characterization of T cell immunodeficiencies could in part be supported by using stable cell lines in which biochemical and molecular studies of the defect could be carried out thereby omitting frequent bleeding of patients. First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells.

A stable IL-2-dependent HVS-transformed T cell line from a CD3γ deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3γ and its phosphorylation are not necessary for internalization. In addition, the abnormal staining pattern of different monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3γ− T cells, the CD3γ chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8+ HVS line from the CD3γ− patient supports the existence of a functional anomaly in his scanty CD8+ peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.