Soluble CD30 and Lymphocyte Activation Gene-3 (CD223), as Potential Serological Markers of T Helper-Type Cytokine Response Induced by Acellular Pertussis Vaccine

Abstract

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...

In Vitro Stem Cell Cultures from Human Dental Pulp and Periodontal Ligament: New Prospects in Dentistry

“…Even if their localization in situ is quite different, DPSCs, SHEDs, PLSCs and BMSCs have many characteristics in common. Isolated in this way, the cells can be cultivated by osteo-inductive culture (29)(30)(31)(32)(33)(34)(35) that can be induced to differentiate in osteogenic pathways by several growth factors, of which BMP-2, for about 4 to 8 weeks. RhBMP-2 is a highly potent osteo-inductive protein that induces bone formation in vivo (36) and osteogenic differentiation in vitro (37)(38)(39)(40)(41)(42).…”

A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells

“…The concentration of serum sLAG-3 is inversely correlated with that of sCD30, a well-established Th2 marker (14). In large series of patients, high levels of serum sLAG-3 have been shown to be associated with resistance to tuberculosis, a disease where Th1 responses are crucial in defense against Mycobacteria (15).…”

Inflammatory cytokines and S-100b protein in patients with hepatitis C infection and cryoglobulinemias

“…About 30% of HCV-infected patients develop circulating cryoglobulins. [3][4][5][6] This may depend on several factors such as duration of chronic infection, virus characteristics (some authors assert that HCV genotype 2a is more frequently associated with MC), or host genetic factors (HLA system, activity of lymphocytes and natural killer cells). The majority of HCV-infected patients with circulating cryoglobulins are either asymptomatic or have nonspecific findings.…”