CD40 Ligand Deficiency

CD40 ligand deficiency (CD40L), currently classified as an inborn error of immunity affecting cellular and humoral immunity, prevalently emerges in boys within the first two years of life. It manifests itself as a decrease in serum IgG, IgA and IgE, with normal or high IgM, defects in T cell proliferation, and decrease in soluble CD40L. These accompany sinopulmonary and/or gastrointestinal infections, and there may be infections caused by pyogenic bacteria, opportunistic infections, autoimmune diseases, and neoplasms. Mild and moderate cases of this deficiency may respond well to prophylactic antibiotic therapy or to human immunoglobulin replacement therapy, in addition to the early treatment of infections. Severe cases can be treated with hematopoietic stem cell transplantation, which allows the healing of such patients, rather than sequelae and a poor progression. Thus, its differential diagnosis with other inborn errors of immunity is essential, especially CD40 deficiency and variable common immunodeficiency; the reason why we have proposed the present literature review

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CD40 Ligand Deficiency.

CD40 ligand deficiency (CD40L), currently classified as an inborn error of immunity affecting cellular and humoral immunity, prevalently emerges in boys within the first two years of life. It manifests itself as a decrease in serum IgG, IgA and IgE, with normal or high IgM, defects in T cell proliferation, and decrease in soluble CD40L. These accompany sinopulmonary and/or gastrointestinal infections, and there may be infections caused by pyogenic bacteria, opportunistic infections, autoimmune diseases, and neoplasms. Mild and moderate cases of this deficiency may respond well to prophylactic antibiotic therapy or to human immunoglobulin replacement therapy, in addition to the early treatment of infections. Severe cases can be treated with hematopoietic stem cell transplantation, which allows the healing of such patients, rather than sequelae and a poor progression. Thus, its differential diagnosis with other inborn errors of immunity is essential, especially CD40 deficiency and variable common immunodeficiency; the reason why we have proposed the present literature review.

Host and bacterial factors affecting induction of immune responses to flagellin expressed by attenuated Salmonella vaccine strains.

Previous observations demonstrated that the delivery of recombinant Salmonella enterica serovar Dublin strains to mice via mucosal routes did not efficiently activate systemic and secreted antibody responses to either type d flagellin or genetically fused heterologous B-cell epitopes, thus reducing the usefulness of the protein as a carrier of epitopes for vaccine purposes. In this work, we investigated murine systemic and mucosal flagellin immunogenicity after oral immunization with attenuated Salmonella strains. The reduced anti-type d flagellin antibody responses in mice immunized via mucosal routes with three doses of flagellated S. enterica serovar Dublin strains were not caused by oral tolerance and could not be restored by coadministration of a mucosal adjuvant. The induction of antibody responses to Salmonella flagellins was shown to differ according to the genetic background, but not the haplotype, of the mouse lineage. Moreover, BALB/c mice orally immunized with S. enterica serovar Typhimurium strains developed anti-type i flagellin sera and secreted antibody responses, which indicated that the serovar of the Salmonella vaccine strain also affected flagellin immunogenicity. Analyses of cytokine responses of BALB/c mice immunized with three oral doses of flagellated S. enterica serovar Dublin vaccine strains showed that, in spite of the lack of antibody responses, elevated type d flagellin-specific CD4-cell-activation-dependent gamma interferon (IFN-gamma) and interleukin-10 responses were elicited after the administration of the vaccine strains via either parenteral or mucosal routes. Similar cytokine production patterns were detected to a T-cell heterologous epitope, derived from the CFA/I fimbriae of enterotoxigenic Escherichia coli (ETEC), in mice orally immunized with a Salmonella vaccine strain expressing hybrid flagella. These results indicate that the immunogenicities of Salmonella flagellins can differ significantly, depending on the murine host and on the bacterial vector used, and demonstrate that the induction of CD4-cell-activation-dependent IFN-gamma production represents a major immune response triggered by flagellin and in-frame fused heterologous T-cell epitopes after the oral administration of recombinant S. enterica serovar Dublin vaccine strains.

Host and Bacterial Factors Affecting Induction of Immune Responses to Flagellin Expressed by Attenuated Salmonella Vaccine Strains

Previous observations demonstrated that the delivery of recombinant Salmonella enterica serovar Dublin strains to mice via mucosal routes did not efficiently activate systemic and secreted antibody responses to either type d flagellin or genetically fused heterologous B-cell epitopes, thus reducing the usefulness of the protein as a carrier of epitopes for vaccine purposes. In this work, we investigated murine systemic and mucosal flagellin immunogenicity after oral immunization with attenuated Salmonella strains. The reduced anti-type d flagellin antibody responses in mice immunized via mucosal routes with three doses of flagellated S. enterica serovar Dublin strains were not caused by oral tolerance and could not be restored by coadministration of a mucosal adjuvant. The induction of antibody responses to Salmonella flagellins was shown to differ according to the genetic background, but not the haplotype, of the mouse lineage. Moreover, BALB/c mice orally immunized with S. enterica serovar Typhimurium strains developed anti-type i flagellin sera and secreted antibody responses, which indicated that the serovar of the Salmonella vaccine strain also affected flagellin immunogenicity. Analyses of cytokine responses of BALB/c mice immunized with three oral doses of flagellated S. enterica serovar Dublin vaccine strains showed that, in spite of the lack of antibody responses, elevated type d flagellin-specific CD4-cell-activation-dependent gamma interferon (IFN-ã) and interleukin-10 responses were elicited after the administration of the vaccine strains via either parenteral or mucosal routes... .