The human polysaccharide- and protein-specific immune response to Streptococcus pneumoniae is dependent on CD4+ T lymphocytes, CD14+ monocytes, and the CD40–CD40 ligand interaction

Abstract

Conti A, et al. Molecular characterization and allergenic activity of Lyc e 2 (beta-fructofuranosidase), a glycosylated allergen of tomato. Eur J Biochem 2003;270:1327-37. 5. Lorenz Y, Enrique E, Lequynh L, Fotisch K, Retzek M, Biemelt S, et al. Skin prick tests reveal stable and heritable reduction of allergenic potency of gene-silenced tomato fruits.The human polysaccharide-and protein-specific immune response to Streptococcus pneumoniae is dependent on CD4 1 T lymphocytes, CD14 1 monocytes, and the CD40-CD40 ligand interactionTo the Editor: Streptococcus pneumoniae is a major cause of pneumonia, septicemia, and meningitis. It causes great morbidity and mortality throughout the world. In particular, young children, the elderly, and immunocompromised individuals are susceptible to pneumococcal infections. Host protection against pneumococcal infections is mediated by antibodies against pneumococcal surface proteins and capsular polysaccharides (caps-PSs). 1 Caps-PSs are a main determinant of virulence of S pneumoniae, and antibodies to caps-PSs are protective against infection with S pneumoniae. Some pneumococcal surface proteins, such as pneumococcal surface protein A (PspA), are also considered virulence factors.Whereas proteins are T lymphocyte-dependent antigens, caps-PSs are considered T lymphocyte-independent type 2 (TI-2) antigens. Although T lymphocytes are not needed for induction of the antibody response to TI-2 antigens, they are involved in the regulation of this antibody response. 2 The role of T lymphocytes in the regulation of the antibody production to TI-2 antigens is poorly understood. Little is known regarding the mechanisms by which intact S pneumoniae elicits protein-and caps-PS-specific antibodies in human subjects. In the present study we immunized humanized mice with severe combined immunodeficiency (SCID) with heat-inactivated S pneumoniae as a model to study the human antibody response to S pneumoniae.To evaluate the role of CD4 1 T cells in the antibody response to pneumococcal caps-PSs and PspA, 6-to 8-week-old SCID mice were treated with TMb1 (an anti-murine IL-2 receptor b-chain antibody used to deplete murine natural killer cells and to improve transplant survival 3 ) and transplanted (in peritoneum) either with PBMCs (containing 4 3 10 6 B lymphocytes, n 5 6) or with PBMCs depleted of CD4 1 cells (by using microbeads; Miltenyi Biotec, Bergisch Gladbach, Germany; n 5 6). After transplantation, the mice were immunized with heat-inactivated S pneumoniae serotype 3 (2 3 10 8 colony-forming units). Two weeks after immunization, antibodies were measured by means of ELISA (with preabsorption of the sera with caps-PS serotype 22F [5 mg/L] for anti-caps-PS). 4,5 SCID/SCID mice reconstituted with PBMCs, but not with PBMCs depleted of CD4 1 cells, produced high levels of IgM and IgG antibodies against caps-PSs and PspA (data not shown; P < .03, Mann-Whitney U test).

Dynamic Change of Lymphocyte-to-Monocyte Is Associated With the Occurrence of POCD After Cardiovascular Surgery: A Prospective Observational Study

“…Previous studies have demonstrated that leucocytes are cellular components of systemic inflammation (Cunningham, 2013). Both lymphocytes and monocytes play important roles in the immune regulatory pathway (Moens et al, 2008). The LMR is a combination of two independent markers of inflammation and was reported to be a potential novel biomarker of inflammatory response (Umehara et al, 2020).…”

Heterogeneidad de las células B de memoria IgM humanas

“…Debido a la dificultad para estudiar ciertas repuestas inmunitarias en humanos, se ha recurrido a los modelos de ratones "humanizados", en los cuales se trasplantan células inmunitarias humanas a ratones inmunodeficientes SCID/ SCID y se los inmuniza con diferentes antígenos. Con uno de dichos modelos, se observó que cuando los ratones recibieron el trasplante de cBm IgM y fueron inmunizados con Streptococcus pneumoniae inactivado o con vacuna contra el neumococo, hubo incrementos en la IgM y en la IgG específicas de antígenos independientes de T, como el lipopolisacárido, o dependientes de T, como las proteínas de la bacteria (Moens, et al, 2008). Con este mismo modelo, se demostró que las cBm IgM humanas trasplantadas conmutaron a IgG y disminuyeron la antigenemia y viremia por rotavirus en los ratones (Narváez, et al, 2012).…”

Production of IgG antibodies to pneumococcal polysaccharides is associated with expansion of ICOS+ circulating memory T follicular-helper cells which is impaired by HIV infection

“…PcPs are T-independent type 2 (TI-2) antigens which, while not requiring T cells for B cell activation, require CD4 + T cells for the regulation of the antibody response, as indicated by dependence on CD40/CD40L interaction [48, 49] and somatic hypermutation of antibody Fab regions, suggesting that GC reactions occur [50]. To investigate the regulation of IgG antibody responses against PcPs, including isotype diversification, by T FH cells, and the effect of HIV infection on this, we examined the production of IgG1 and IgG2 antibodies in HIV seronegative subjects and HIV patients (ART-treated and -naive) following vaccination with unconjugated PcPs.…”