Human mast cells modulate proliferation and cytokine production by CD8+ T lymphocytes.
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Biomedical subjects
Publications and source records attributed to T A Out.
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OBJECTIVE: To explore further the mechanisms leading to immune deficiency in chronic renal failure and the role of dialysis treatment in these mechanisms. DESIGN: Cross-sectional and longitudinal analysis. PATIENTS: We studied 39 children treated with peritoneal dialysis (PD), 23 children treated with hemodialysis (HD), 33 children not yet dialyzed [chronic renal failure (CRF)], and 27 healthy children. Peritoneal cells were also obtained from PD children for analysis. METHODS: White blood cells (WBCs) were isolated from blood and peritoneal dialysis effluent by centrifugation. The number of CD2+, CD4+, and CD8+ T cells, B cells, and natural killer cells were measured by flow cytometry. RESULTS: The total peripheral blood lymphocyte count was lower in PD children (2.6 x 10(9)/L), HD children (2.1 x 10(9)/L), and CRF children (2.0 x 10(9)/L) compared with healthy children (3.1 x 10(9)/L, p < 0.05). The B lymphocyte count was also lower in PD children (0.34 x 10(9)/L), HD children (0.22 x 10(9)/L), and CRF children (0.33 x 10(9)/L) compared with healthy children (0.52 x 10(9)/L, p < 0.01). Numbers of CD4+ T cells were not different, but numbers of CD8+ T cells were lower in PD children (0.56 x 10(9)/L), HD children (0.63 x 10(9)/L), and CRF children (0.53 x 10(9)/L) compared with healthy children (0.77 x 10(9)/L, p < 0.05). The count of natural killer cells was lower in PD children (0.21 x 10(9)/L), HD children (0.17 x 10(9)/L), and CRF children (0.18 x 10(9)/L) compared with healthy children (0.50 x 10(9)/L, p < 0.0001). The CD4/CD8 ratio of lymphocytes in peritoneal effluent was 0.8 versus 1.9 in peripheral blood (p < 0.001). The CD2/CD19 ratio was not different. The cell subsets remained stable during the first year of PD treatment. The CD2/CD19 ratio in peritoneal effluent was higher in children with a peritonitis incidence > or = 1 per year. CONCLUSIONS: The reduced numbers of B lymphocytes, CD8+ T cells, and natural killer cells found in CRF children, dialyzed or not, may favor the frequent occurrence of infections.
In patients suffering from recurrent or chronic infections with encapsulated bacteria the humoral immune disorder of IgG subclass deficiencies is common (about 20%), yet insufficiently diagnosed because of the nonspecific symptomatology and the often unaffected levels of total immunoglobulin (Ig) isotypes. IgG subclass deficiency is correctly diagnosed by measurement of all four IgG subclasses. The IgG2-subclass deficiency is most frequent, often together with decreased IgG4- and/or IgA-levels. The IgG2-subclass deficiency is associated with a diminished immune response to (bacterial capsular) polysaccharide antigens. Although the anti-polysaccharide response is generally believed to be IgG2-restricted, a causal relationship between a decrease in IgG2 and disease is obscure. First, the precise meaning and contribution of IgG2 to the opsonization of encapsulated microorganisms is incompletely known. Second, several healthy individuals completely lack one or more isotype/subclasses due to (pseudo-) deletions of the genes, but still produce protective antibody titers in the residual Ig isotype or subclass. Third, young children mount protective titers of specific IgG1 antibodies against polysaccharides, whereas IgG2-subclass deficient children are prone to infection by encapsulated bacteria. In sum, decreases in IgG2 subclass levels may be merely epiphenomenal in a large group of patients who do not respond effectively to (bacterial) polysaccharides. New directions of investigation in order to obtain insight in the prevalence and pathogenesis of IgG subclass deficiencies are discussed.