Bystander T cell activation in common variable immunodeficiency.

Hatfield-Green M, Wong G.K.Y, Guckian M, Jones J, Clifford H, Huissoon A.P.

Department of Immunology, Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UK.

Introduction/Aims: Numerical and functional T cell abnormalities are commonly associated with common variable immune deficiency (CVID). Both antigen specific and antigen non-specific (bystander) T cell proliferation are detectable during normal immune responses. Bystander T cell activation is implicated in tissue damage in some autoimmune diseases and infections. We therefore examined bystander T cell activation in patients with CVID.

Methods: 12 CVID patients and 12 healthy controls were recruited. PBMC were isolated and then stimulated with TCR V-beta 7 or 12 antibodies and cultured for 5 days. On day 5, PBMC were harvested and labelled with anti-CD3, CD25, CD71 and V beta 7 or V beta 12 fluorescenct antibodies. Bystander T cell activation was determined by measuring the expression of surface activation markers on cells not directly stimulated by TCR V-beta antibodies. A bystander activation score of 0-4 was assigned. The scores were then co-examined with patients clinical and B cell phenotype.

Results:  Reduction in bystander activation was seen in CVID when TCRV?12 stimulated cells were stained with CD71 (p=0.1659). 3 out of 4 patients with autoimmunity had a high[AP1] bystander response score. All 5 patients with high[AP2] bystander response score had bronchiectasis. No correlations between bystander activation score and B cell immunophenotyping were observed.

Conclusion:  Our data suggested that bystander T cell activation is reduced in CVID under certain in vitro stimulatory conditions. Despite low patient numbers interesting correlations between bystander responses and clinical phenotype were observed. Higher level of bystander activation in the CVID group is associated with higher incidence of bronchiectasis and autoimmunity[AP3].

Key words: CVID, common variable immunodeficiency, T cell bystander activation, TCR V beta, EUROclass