| Abstrakt: |
Clonal T cell expansion requires simultaneous activation of the TCR and secondary signals, e.g. CD2, CD4, CD28. Interference of CD2/CD58 interaction with MoAbs abrogates the primary immune response and antibody production. Given this functional importance of CD2/CD58 interaction for the generation of specific immune responses, we demonstrate for the first time a defective CD2 pathway activation in patients with CVID (seven children and four adults). The co-stimulatory effect of monocytes upon CD2-triggered proliferation was significantly impaired in CVID patients: 4080 ct/mm versus 20.769 ct/mm in controls (P<0M5). Second, IL-I, which is a strong comitogenic factor for activation via CD2 in normal T cells, showed a defective amplifier function of the CD2 pathway in most patients (median 1.714 ct/mm in patients versus 17.52l ct/mm in controls; P < 0.05). In addition, by using a mitogenic combination of CD2 plus CD45 MoAb, median proliferation of T cells was severely depressed in patients: 10.577 ct/mm versus 34685 ct/mm in controls (P = 0005). In conclusion, the marked dysfunction seen in responsiveness to phytohaem-agglutinin (PHA) (median 24.594 ct/mm in patients versus 52229 ct/mm in controls; P<0001) and after CD2 triggering, together with the unaffected response to TCR-CD3, suggest that the T cell deficiency in CVID is in part due to deficiencies in the CD2 pathway. Since direct activation of protein kinase C (PKC) by phorbol ester restores defective T cell responses to normal, our results suggest that an early signal-transducing defect might exist at a step proximal to PKC activation in patients with CVID. [ABSTRACT FROM AUTHOR] |
