Characterization of Herpesvirus saimiri-transformed T lymphocytes from common variable immunodeficiency patients

SUMMARY

Common variable immunodeficiency (CVID) is a very frequent but heterogeneous syndrome of antibody formation. The primary defect remains unknown, but many reports describe peripheral blood T lymphocyte dysfunctions in a substantial proportion of CVID patients, which may impair T–B cell collaboration. In order to investigate whether such putative defects were intrinsic to T cells or, rather, secondary to quantitative differences in T cell subset distribution, or to other described disorders, we have used Herpesvirus saimiri (HVS) for the targeted transformation of CVID CD4⁺ and CD8⁺ T cells and subsequent functional evaluation by flow cytometry of their capacity to generate cell surface (CD154, CD69) or soluble (IL-2, TNF-α, IFN-γ) help after CD3 engagement. Unexpectedly, the results showed that 40 different CVID blood samples exposed to HVS gave rise with a significantly increased frequency to transformed CD4⁺ T cell lines, compared to 40 age-matched controls (27%versus 3%, P≤ 0·00002) suggesting the existence of a CVID-specific signalling difference which affects CD4⁺ cell transformation efficiency. The functional analysis of 10 CD4⁺ and 15 CD8⁺ pure transformed T cell lines from CVID patients did not reveal any statistically significant difference as compared to controls. However, half of the CD4⁺ transformed cell lines showed CD154 (but not CD69) induction (mean value of 46·8%) under the lower limit of the normal controls (mean value of 82·4%, P≤ 0·0001). Exactly the same five cell lines showed, in addition, a significantly low induction of IL-2 (P≤ 0·04), but not of TNF-α or IFN-γ. None of these differences were observed in the remaining CD4⁺ cell lines or in any of the transformed CD8⁺ cell lines. We conclude that certain CVID patients show selective and intrinsic impairments for the generation of cell surface and soluble help by CD4⁺ T cells, which may be relevant for B lymphocyte function. The transformed T cell lines will be useful to establish the biochemical mechanisms responsible for the described impairments.