DIFFERENTIAL USAGE OF T-CELL RECEPTOR V-BETA GENE FAMILIES BY CD4(-CELLS IN PATIENTS WITH CD8(HI) COMMON VARIABLE IMMUNODEFICIENCY - EVIDENCE OF A POSTTHYMIC EFFECT() AND CD8(+) T)

In this study, we report that differences between T-cell receptor (TCR ) V beta gene family usage in CD4(+) and CD8(+) T cells are significan tly greater in a subgroup of patients with common variable immunodefic iency (CVI) and high levels of activated CD8(+) T cells (CD8(hi) CVI) than in controls (P < 0.001). In CD8(hi) CVI patients, such difference s were also significantly greater for V beta 12 than for other V beta families. As the causes of the differential usage of V beta gene famil ies by CD4(+) and CD8(+) T cells are under investigation, it was inter esting that the combined differences between V beta gene family usage in the CD4(+) and CD8(+) T-cell subpopulations as a whole were signifi cantly lower than the combined differences between individual V beta g ene family usage in either CD4(+) or CD8(+) T-cell subpopulations (P < 0.001 in both control and CD8(hi) CVI patients). Further, the pattern of V beta gene family usage in CD4(+) T cells was remarkably similar to that in CD8(+) T cells in both groups. These data strongly suggest that differences in V beta gene family usage arising from coselection by major histocompatibility complex (MHC) class I versus MHC class II restriction elements do not fundamentally distort 'basic' V beta gene family usage patterns. They also support the concept that differences in CD4(+) and CD8(+) T-cell V beta gene family usage, which were incre ased in CD8(hi) CVI, can arise from high-affinity interactions between disease-associated antigens or superantigens and T cells in the post- thymic T-cell compartment.