Ineffective expression of CD40 ligand on cord blood T cells may contribute to poor immunoglobulin production in the newborn

Brugnoni, Duilio; Airò, Paolo; Gralfu, Daniel; Marconiu, Massimo; Lebowitzu, Morena; Plebaniu, Alessandro; Gilianiu, Silvia; Malacarne, Fabio; Cattaneo, Roberto; Ugaziou, Alberto G.; Albertini, Alberto; Kroczeku, Richard A.; Notarangelo, Luigi D.

doi:10.1002/eji.1830240831

Cited by 96 publications

(41 citation statements)

References 32 publications

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“…It is generally regarded as an activation marker (28). However, we and others (1,27,29,30) did not find other markers of activation in neonatal cord or infant blood, such as increased expression of CD25, HLA-DR, CD69, and CD154 (CD40 ligand). Nor did we find an increase of thymocyte-like CD1a ϩ or CD4 ϩ /CD8 ϩ double-positive T cells.…”

Section: Discussioncontrasting

confidence: 61%

Longitudinal Survey of Lymphocyte Subpopulations in the First Year of Life

et al. 2000

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Age-matched reference values for lymphocyte subpopulations are generally obtained via cross-sectional studies, whereas patients are followed longitudinally. We performed a detailed longitudinal analysis of the changes in lymphocyte subpopulations in a group of 11 healthy infants followed from birth up to 1 y of age, with special attention for early developmental markers, markers of maturation, and markers of activation. We found that T and B lymphocytes increased at 1 and 6 wk of age, respectively. In contrast, NK cells showed a sharp decline directly after birth, suggesting that they are more important during pregnancy than thereafter. CD45RAϩ -mainly CD4 ϩ -naive T lymphocytes were high at birth, and increased further during the first year of life; they form a large expanding pool of cells, ready for participation in primary immune responses. The absolute counts of CD45RO ϩ memory T lymphocytes were similar in infants and adults, albeit with a lower level of expression of CD45RO on infant T lymphocytes. Almost all infant T lymphocytes expressed CD38 throughout the first year of life. The abundant expression of CD38 on an infant's T lymphocytes might be related to a greater metabolic need of the large population of naive untriggered cells that are continually involved in primary immune responses during the first year of life. The high B lymphocyte counts in infants mainly concerned CD38 ϩ B lymphocytes throughout the first year of life. Also, the relative frequencies of CD1c ϩ and CD5 ϩ B lymphocytes were higher throughout the first year of life than in adults. Therefore, CD1c, CD5, and CD38 could be markers of untriggered B lymphocytes. Immunophenotyping of blood lymphocyte subpopulations is an important tool in the diagnosis and follow-up of children with immune disorders. Correct interpretation of the obtained results requires knowledge of the normal development of the immune system during the first years of life.For this purpose, several sets of age-matched reference values of relative frequencies and absolute counts of lymphocyte subpopulations in childhood have been reported (1-5). Because of the higher blood lymphocyte counts in neonates and infants compared with adults (1, 6), differences in lymphocyte subpopulations are better reflected by comparison of absolute counts than relative frequencies. In that way, trends are observed that are missed when only relative frequencies are used (1). These absolute lymphocyte counts are more accurately determined by the lysed whole blood technique than by analysis after density gradient separation (7,8).To date, age-matched reference values for lymphocyte subpopulations were all obtained in cross-sectional studies. Longitudinal studies in individual children are more informative about the pattern of lymphocyte subpopulation development as a function of time. Children with immune disorders are also followed longitudinally. Therefore, it is useful to compare patient data with data from studies on longitudinal development of lymphocyte subpopulations in healthy childr...

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Section: Discussioncontrasting

confidence: 61%

Longitudinal Survey of Lymphocyte Subpopulations in the First Year of Life

et al. 2000

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“…Are the cells functionally mature but have no antigenic exposure? Previous findings implicate low or absent CD40L expression on T cells as one of the key factors, since CD40-CD40L interactions are necessary for both B-cell activation and isotype switching [6]. It has also been shown that cord blood T cells are poor producers of certain cytokines which play a major role in isotype switching [19].…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin‐Secreting Cells in Cord Blood: Effects of Epstein–Barr Virus and Interleukin‐4

et al. 1999

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Gudmundsson KO, Thorsteinsson L, Gudmundsson S, Haraldsson Á . Immunoglobulin-Secreting Cells in Cord Blood: Effects of Epstein-Barr Virus and Interleukin-4. Scand J Immunol 1999;50:21-24 The contribution of cord blood B lymphocytes to the immune response has been under considerable investigation. Cord blood B cells produce almost no antibodies except of the immunoglobulin (Ig)M isotype, indicating immaturity of the cells or the environment they reside in. The aim of this study was to investigate the number of circulating IgA-, IgM-, IgG-, and IgE-producing cells in cord blood in comparison to adult peripheral blood using the ELISPOT method. Moreover, we studied the effect of transformation with the Epstein-Barr virus (EBV) on the proportion of cells producing different isotypes with or without interleukin (IL)-4. Cord blood had IgM-producing cells circulating predominantly, but also some IgA-and IgG-producing cells, whereas adult peripheral blood contained high amounts of circulating IgA-producing cells and some IgM-and IgG-producing cells. No circulating IgE-producing cells were found in either group. Transformation by EBV caused significant expansion of IgA-, IgM-, and IgG-producing cells in adult peripheral blood, but almost only of IgM-producing cells in cord blood. A low but detectable expansion of IgA-and IgG-producing cells was found. Cells producing IgE were still not found, even after EBV transformation. However, EBV transformation in the presence of IL-4 increased the numbers of IgE-producing cells significantly both in cord blood and adult peripheral blood. These findings indicate that cord blood contains some circulating IgA-and IgG-producing cells that are expanded to some extent after EBV infection. They also indicate that cord blood B cells have a similar capacity for IgE production to adult peripheral blood B cells when appropriately stimulated.

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“…There appears to be a reduced incidence and severity of acute or extensive chronic graft-vs-host disease (GVHD) in CB transplantation (CBT) when compared with results obtained using PB and BM (22)(23)(24). Accumulating results suggest that reduced incidence and severity of GVHD in CBT may involve an inactivation of donor-derived CB T cells with respect to the secretion of proinflammatory cytokines as well as killing activity due to the expressions of perforin and Fas ligand (17,(25)(26)(27)(28). Clinical manifestations suggested that transplanted T cells derived from BM and PB inoculum may be activated, while transplanted CB T cells may exhibit inactivated status following stimulation with allogeneic Ag and various cytokines (17,(22)(23)(24)29).…”

Section: Mip-1␣ and Rantes As Compared With That Of Cd45romentioning

confidence: 99%

Chemokine Receptor Expressions and Responsiveness of Cord Blood T Cells

Sato¹,

Kawasaki

Nagayama³

et al. 2001

The Journal of Immunology

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Chemokines and their receptors play a critical role in the selective attraction of various subsets of leukocytes. We examined the chemokine receptor expressions and responsiveness of cord blood (CB) T cells. Flow-cytometric analysis revealed that peripheral blood (PB) T cells expressed CCR-1, CCR-2, CCR-5, CCR-6, CXC chemokine receptor-3 (CXCR-3), and CXCR-4, while CB T cells expressed only CXCR-4 on their surface. Chemotactic migratory response of CB T cells to macrophage-inflammatory protein (MIP)-1α, monocyte chemoattractant protein-1, RANTES, MIP-3α, monokine induced by IFN-γ, and IFN-γ-inducible protein-10 was significantly impaired compared with those of PB T cells. In contrast, the ability of CB T cells to migrate to MIP-3β, 6Ckine, and stromal cell-derived factor-1α was greater than that of PB T cells, and these events were correlated with the expression levels of CCR-7 and CXCR-4, respectively. Engagement of CD3 and CD28 specifically up-regulated CXCR-3 expression and chemotaxis to monokine induced by IFN-γ and IFN-γ-inducible protein-10, whereas this stimulation down-regulated CCR-7 expression and chemotaxis to MIP-3β and 6Ckine in PB T cells, but not in CB T cells. These results suggest that PB T cells and CB T cells exhibit distinct chemokine responsiveness via different chemokine receptor repertoire.

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Ineffective expression of CD40 ligand on cord blood T cells may contribute to poor immunoglobulin production in the newborn

Cited by 96 publications

References 32 publications

Longitudinal Survey of Lymphocyte Subpopulations in the First Year of Life

Longitudinal Survey of Lymphocyte Subpopulations in the First Year of Life

Immunoglobulin‐Secreting Cells in Cord Blood: Effects of Epstein–Barr Virus and Interleukin‐4

Chemokine Receptor Expressions and Responsiveness of Cord Blood T Cells

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