T cell subsets in rheumatic fever in New Caledonia

T cell subsets were evaluated in 76 New-Caledonian patients with recent onset rheumatic fever. A significant but modest decrease of OKT4+ cells and increase of OKT8+ cells was noted, leading to a decreased OKT4/OKT8 ratio. These changes were observed irrespective of the presence of carditis.     

Experimental IgG antibody production in vitro by peripheral blood and tonsil surface gamma+ B lymphocytes from Plasmodium falciparum-immune West Africans

Antigen reactive B cells in tonsil specimens from teenagers from a region moderately exposed to P. falciparum were capable of being differentiated in vitro and producing specific immunoglobulin (Ig)G in up to 33% of individual experiments. Mononuclear cells or purified (s)gamma+ CD19+ B cells from peripheral blood or tonsil specimens from P falciparum-immune Senegalese subjects produced antigen-specific IgG upon appropriate stimulation in vitro. One fraction of this IgG was produced de novo by differentiated B cells and another fraction was likely bound on the surface of circulating or resident CD19+ sgamma+ B cells which were found in significantly greater numbers in individuals from rural Senegal as compared to nonimmune European controls. This study further documents the baseline levels of in vitro driven anti-P. falciparum IgG antibody production by mononuclear cells from blood and tonsils in immune populations exposed to P. falciparum differentially. Furthermore, this study demonstrates the relevance and potential utility of tonsils as a source of B lymphocytes to characterize further specific antibody responses to P. falciparum antigens in immune populations.     

Gender-dependent specific immune response during chronic human Schistosomiasis haematobia

The cellular and humoral acquired immune responses to Schistosoma haematobium 28 kD gluthathione S-Transferase (Sh28GST) antigen were evaluated in a Senegalese population chronically infected with S. haematobium parasite. We show a gender-dependent immune response in adult individuals presenting similar intensities of infection. Indeed, the specific IgA response and production of TGF-beta and IL-10 were found significantly higher in females compared to males. In addition, we showed that this profile was combined with a weak production of Th1-related cytokines (TNFalpha and IFNgamma) and was associated with an absence of proliferation to the antigen. A significantly higher Nuclear Matrix Protein 41/7 secretion, an apoptosis marker, was specifically observed in mononuclear blood cell cultures of females suggesting that a specific cell death process was engaged in a gender-dependent manner. This specific profile could be associated with the so-called T helper type-3 (Th3) immune response specifically promoting the production of IgA and would be developed upon the down-regulation of the specific Type-1 response by a probable cell death mechanism. This gender-dependent immune regulation, which may be under the influence of nonimmunological factors like sexual hormones, may be related to the chronicity of the infection.     

Secretion of parasite-specific immunoglobulin G by purified blood B lymphocytes from immune individuals after in vitro stimulation with recombinant Plasmodium falciparum merozoite surface protein-119 antigen

The C-terminal 19 000 MW fragment of merozoite surface protein-1 (MSP1₁₉) is one of the most promising candidate antigens for a malaria vaccine. Baculovirus recombinant Plasmodium falciparum MSP1₁₉ has been used to define conditions for the in vitro production of specific antibodies by purified human blood B cells in a culture system where T-cell signals were provided by the engagement of CD40 molecules and exogenous cytokines. MSP1₁₉ preferentially induced surface immunoglobulin G (IgG) -positive (sγ⁺) B lymphocytes from P. falciparum-immune donors to differentiate and produce antigen-specific IgG. In contrast, naïve B cells or cells from non-immune donors could not be induced to secrete parasite-specific IgG in vitro. Although IgG secretion was obtained in the absence of exogenous cytokines, it was dependent on B-cell-derived interleukin-10 (IL-10) and/or B-cell factor(s) under the control of IL-10, since IgG levels were significantly decreased in the presence of neutralizing anti-IL-10 antibodies. These results demonstrate at the cellular level that a single malaria vaccine candidate polypeptide can direct parasite-specific antibody production mediated by the secretion of potentiating factors.     

Flow cytometry identification and characterization of mononuclear cell subsets in the neotropical primate Saimiri sciureus (squirrel monkey)

BACKGROUND: The neotropical primate squirrel monkey is used in many areas of biomedical research including neuroendocrinology, immunology and infectious diseases. However, research has been hampered by the lack of immunological tools for this primate. METHODS: A series of 67 commercially available monoclonal antibodies to human CD antigens or cytokines were tested on Saimiri mononuclear cells and the specificity was assessed by double staining using flow cytometry. RESULTS: Monoclonal antibodies defining the main mononuclear cells subsets (monocytes, B, T, including CD4 and CD8 T cells) as well as activation markers have been identified. The conditions to specifically identify the various cell subsets using two color flow cytometry and establish their relative proportions have been set-up. We also have established normal values of the main circulating mononuclear cell subsets for adult Saimiri sciureus monkeys from the breeding unit of Institut Pasteur in French Guiana. The distribution between spleen, blood and lymph nodes has been compared. CONCLUSIONS: These tools allow documenting the phenotype of most Saimiri mononuclear cell subsets and assessing their activation level. This opens new perspectives for vaccinology and immunopathology research in this experimental non-human primate host, in particular for malaria research.     

Differential production in vitro of antigen specific IgG1, IgG3 and IgA: a study in Schistosoma haematobium infected individuals

This study has evaluated the individual control of isotype production and the influence of external signals that can be experimentally provided in vitro, in antibody responses to two different recombinant Schistosoma antigens (Sh28GST and TPx-1). Peripheral blood mononuclear cells or enriched B cell fractions obtained from S. haematobium infected Senegalese adults were induced to terminal differentiation in vitro. The production of antibody to either antigen was donor-dependent and for each donor it was antigen-dependent. Differentiation to IgG1 and IgG3 production, and possibly IgA, specific to these conserved parasite antigens could be regulated differentially in vitro. Exogenous IL-2 and IL-10 or IL-10 and TGF-beta led to the production of specific IgG3 or IgG1 and/or IgA, respectively. This is the first report on such experimentally induced differential regulation of antigen-specific IgG1 and IgG3. This may have implications in designing protocols for protein based-vaccinations aiming at eliciting antibody responses of certain protective-type isotypes.     

Are all therapeutic plasma preparations the same: Is it worth assessing them in clinical trials?

Contrary to what is generally considered, plasma for direct therapeutic use is all but “standard” and can be made using a multitude of variable processes differing from one preparation to another; in sum, those changes make the final component inhomogeneous especially within inter-blood bank comparisons. The variability is further multiplied by the donors’ genetic polymorphisms. This is rarely addressed in the clinical trials and meta analyses, though this may have impact on clinical outcome in patients. This short review encompasses the variability parameters in the processing of therapeutic plasma and advocates for novel, prospective, trials to assess which type of plasma is the most beneficial to patients in need, as this type may differ depending on the patients’ pathological condition.