In addition to its catalytic activities as ecto-NAD+ glycohydrolase (NADase), CD38 displays the ability to transduce signals of biological relevance. Indeed, ligation of CD38 on peripheral blood mononuclear cells (PBMC) by agonistic monoclonal antibodies (mAbs) is followed by the transcription and secretion of a vast array of regulatory cytokines. The present work addresses the issue of whether the signals leading to calcium (Ca2+) mobilization, lymphocyte proliferation and release of cytokines is dependent on the epitopes recognized by the individual mAbs. Competition binding analysis identifies two families of mAbs, namely IB4, IB6 and AT2 on one side and OKT10, SUN-4B7 and AT1 on the other. Each mAb family binds epitopes that are completely or partially common. However, the functional activities of the CD38 molecule can not be simply attributed to the epitopes engaged: for instance, IB4 and OKT10 mAbs, which bind different epitopes, perform as agonistic mAbs in inducing PBMC proliferation and interferon (IFN)-gamma secretion. SUN-4B7 yields intermediate effects, whereas IB6, AT1 and AT2 mAbs are totally ineffective. The effects mediated by IB4 and OKT10 mAbs are apparent in 80% of the healthy individuals studied, whereas the effects of SUN-4B7 mAb operate only in 25% of the donors. Interleukin (IL)-6 secretion was observed in all individuals analyzed, irrespective of the epitopes triggered and of mAbs used to ligate the CD38 molecule. In addition, IB4 is the only mAb able to induce significant intracellular Ca2+ fluxes.

T cell responses are involved in vaccine-induced immunity to pertussis but no easy-to-monitor, serological markers are available to assess these responses. The lymphocyte activation gene-3 (CD223) molecule is present on, and released by, activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with Th2 immune responses. Starting from the recent knowledge of the cytokine profile induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria-tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The correlation of the two proteins with specific antibody and T cell responses was assessed. The main findings are: i) sCD223 and sCD30 levels are inversely related, suggesting that the two markers are the expression of different and counter-regulated T-cell responses; ii) sCD30 level correlated with induction of T cell proliferation to pertussis vaccine antigens and antibody response to pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate markers to assess the induction of Th-type responses in vaccine recipients.The mechanisms underlying induction of immune protection from Bordetella pertussis infection are not completely understood (I). Data from experimental infections and, in part, clinical studies suggest that natural immunity as well as T and B memory cell compartments are involved, but the differential contribution of each of these components in the protection induced by vaccination or disease-free natural exposure to B. pertussis or the disease itself remains largely undetermined (1-10). A correlation between high titers of antibodies against some B. pertussis antigens and protection of household contacts ofpertussis cases has been found (11-13), nevertheless, no direct correlation between serum antibody levels and protection from pertussis was found in several clinical trials with extended, carefully investigated, follow-up periods (14)(15)(16)(17)(18).Since the discovery of T helper (Th)l and Th2 lymphocyte subsets and their role in the regulation of immune response, studies have been intensely focused on the possibility of discriminating the prevalent expansion of CD4 lymphocytes with Th I or Th2 profile, in consideration to the differential role of each subset for vaccine efficacy. Thl .or Th2 are mainly discriminated through the pattern of their secreted cytokines, in that Thl subsets secrete interferon gamma (IFN-y) but not IL-4, while Th2 subsets secrete IL-4, IL-5, IL-6, IL-1O and IL-13 but not IFN-y However, a mixed pattern of cytokines is often secreted by a CD4 subset defined as .In the specific case of pertussis vaccines, the complexity of the mechanisms underlying immune protection following vaccination is demonstrated by the observation that equally protective primary vaccinations such as those achieved by whole cell (wP) or acellular (aP) vaccines induce different Th cytokine profiles (3,(6)(7)(9)(10). Particularly, our previous data fr...