Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID)

The proliferative responses of T lymphocytes of a subset of patients with C VID are abnormally low. This may be due to abnormalities in extracellular i nteractions or signalling defects downstream from membrane-associated recep tors. Demonstrating that the T cell receptor signalling was normal, we obse rved no abnormal pattern of activation-induced tyrosine phosphorylation in cells from CVID patients. Moreover, the addition of exogenous IL-2 increase d the low proliferation to mitogens, thus indicating the integrity of the I L-2R signalling apparatus. Attractin is a rapidly expressed T cell activati on antigen involved in forming an association between T cells and monocytes . Twenty-four to 48 h after activation by CD3 cross-linking, attractin expr ession was not up-regulated on the cells of CVID patients despite normal up -regulation of CD25 and CD26. On control cells, however, attractin expressi on was up-regulated together with CD25 and CD26. The addition of the purifi ed 175-kD attractin was capable of restoring the proliferative response of peripheral blood mononuclear cells following CD3 X-L in the presence of sub optimal concentrations of rIL-2 (10 and 20 U/ml). The effect was dose-depen dent with the maximal effect at a concentration of 500 ng/ml, and present a t a concentration as low as 50 ng/ml. Due to the likely role of attractin i n cell guidance and amplification of the immune response, our results indic ate that the lack of up-regulation of the molecule in patients with CVID ma y in turn affect any further step of productive immune response. Our findin g may also imply a potential therapeutic role for this novel molecule.