Diminished expression of CD40 ligand by activated neonatal T cells.

Abstract

CD40 and CD40 ligand (gp39) mediate contact-dependent T-B cell interaction. We determined the expression of CD40 ligand by activated neonatal T cells and the response of neonatal B cells when activated through CD40. Although expression of CD40 ligand peaked simultaneously in both activated adult and neonatal cells, neonatal T cells expressed significantly less CD40 ligand surface protein and mRNA than adult T cells. Activated thymocytes also expressed far less CD40 ligand than adult T cells. Consistent with these results, activated neonatal T cells exhibited less helper function than activated adult T cells. Neonatal T cells primed and restimulated in vitro expressed CD40 ligand in amounts comparable with adult T cells and provided B cell help more effectively. This suggests that the poor expression of CD40 ligand reflects antigenic naiveté rather than an intrinsic defect of neonatal T cells. Neonatal B cells cultured with soluble CD40 ligand (sgp39) and IL-10 produced IgM in amounts comparable with adult cells, but much less IgG and IgA. Nevertheless, neonatal B cells were capable of proliferation and class switching, since sgp39 and IL-4 induced proliferation and IgE production comparable to adult B cells and production of modest amounts of IgG. Together, these results indicate that diminished CD40 ligand expression, along with decreased production of lymphokines, may be responsible, at least in part, for the transient immunodeficiency observed in human neonates.

Down-regulation of Th1 responses in human neonates

“…Human neonates are not able to mount an efficient immune response to a large number of pathogens [for reviews see [5][6][7][8]. The immaturity of the immune system at birth involves regulatory defects in the production of IgG, but IgG antibodies passively acquired from the mother assure high level of humoral immunity against extracellular bacteria [9,10]. Regulatory defects of cell-mediated immunity against intracellular pathogens, however, are not compensated by maternally derived factors.…”

IL‐18 time‐dependently modulates Th1/Th2 cytokine production by ligand‐activated NKT cells

“…The CD28 costimulatory pathway also interacts with the CD40-CD154 costimulatory pathway and regulates Th1/Th2 immune responses [20]. IL-18 injection induces CD154 expression on CD4 + T cells [30], and the maximum levels of CD154 expression are observed between 6 h and 8 h after activation of T cells [30,31].…”

CD40, autophagy and Toxoplasma gondii

“…CD40-induced autophagic killing of T. gondii may be an important contributor to control of T. gondii in humans because CD40 induces killing of T. gondii independently of IFN-γ, STAT1, NOS2 and IRG (Andrade et al 2005a, Subauste et al 2007a. Defects in the CD40 pathway are likely relevant to at least three groups of patients that develop cerebral and/or ocular toxoplasmosis: patients with X-linked Hyper IgM syndrome who lack functional CD154 (Subauste et al 1999), newborns since neonatal CD4 + T cells exhibit impaired expression of CD154 (Durandy et al 1995, Nonoyama et al 1995, Julien et al 2003, Han et al 2004, Kaur et al 2007) and neonatal dendritic cells have reduced levels of CD40 (Kaur et al 2007). Impaired CD154 induction is particularly more pronounced in preterm babies (Kaur et al 2007), a finding relevant to toxoplasmosis in newborns since this is an infection acquired prior to birth.…”