HERPES-VIRUS SAIMIRI TRANSFORMATION OF T-CELLS IN CD3-GAMMA IMMUNODEFICIENCY - PHENOTYPIC AND FUNCTIONAL-CHARACTERIZATION

The characterization of T cell immunodeficiencies could in part be sup ported by using stable cell lines in which biochemical and molecular s tudies of the defect could be carried out thereby omitting frequent bl eeding of patients. First attempts to obtain such cell lines included HTLV-1 transformation and exogenous IL-2 administration, but both mode ls have important disadvantages. Recently, a virus isolated from the s quirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transfor med T cell line from a CD3 gamma deficient patient has been obtained; and this cell line displays both the phenotypic and the functional cha racteristics of the patient's lymphocytes. Moreover, the line down-mod ulates TCR/CD3 surface expression upon CD3 engagement, as do the patie nt's lymphocytes, showing that CD3 gamma and its phosphorylation are n ot necessary for TCR/CD3 internalization, In addition, the abnormal st aining pattern of different anti-TCR/CD3 monoclonal antibodies is pres erved in the HVS-patient line. Since HVS is capable of transforming CD 3 gamma(-) T cells, the CD3 gamma chain does not seem to be involved i n the HVS receptor process. The fact that it is not possible to obtain a CD8(+) HVS line from the CD3 gamma(-) patient supports the existenc e of a functional anomaly in his scanty CD8(+) peripheral lymphocytes, Thus, HVS transformation is a suitable model for T cell immunodeficie ncy studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.