Antigen‐specific plaque‐forming cell response of human cord blood lymphocytes after in vitro stimulation by T cell‐dependent antigens

Abstract

Mononuclear cells isolated from human cord blood (CBL) of full-term neonates were stimulated in vitro with a dose range of T cell-dependent antigens, i.e. ovalbumin or sheep erythrocytes, and tested for the capacity to mount an antigen-specific plaque-forming cell (PFC) response. Both of the antigens used induced in CBL a PFC response with the same kinetics of PFC formation and of the same magnitude as found in cultures of adult peripheral blood lymphocytes (PBL). However, optimal PFC responses in CBL were obtained at a hundredfold lower concentration of the antigens compared with the optimal antigen doses for the induction of a PFC response in adult PBL. This phenomenon was further investigated with respect to the antigen dose dependency of the activation of neonatal B cells and neonatal regulatory T cells. The induction of a PFC response in CBL at antigen concentrations that were suboptimal for adult PBL showed a correlation with the particular antigen dose requirements for the activation of B cells and T helper cells in neonates. Furthermore, the findings suggest that the decrease of the PFC response in CBL stimulated with supraoptimal doses of antigen was not caused by the induction of unresponsiveness at the B cell level or by interference of pregnancy-associated substances with the PFC response, but was rather the result of the activation of antigen-specific T suppressor cells. Neonatal T suppressor cells were activated at antigen concentrations that generated T helper activity in the adult. Thus, although neonatal B cells possess the intrinsic capacity to mature into antigen-specific PFC, the conditions for effective activation of neonatal T cells regulating the B cell response differ from those for the activation of adult regulatory T cells.

Human T-lymphocyte response in vitro to synthetic peptides of herpes simplex virus glycoprotein D.

“…Indeed, a recent report shows that suppressor T cells are induced in neonatal mononuclear cell cultures at antigen concentrations that induce helper cells in adult cultures (38). The suppressor cells' inability to proliferate in response to antigen is analogous to murine suppressor effector T-cell lines against human gamma globulin, shown by Levich et al (39) to be inducible by but nonresponsive to human gamma globulin in a proliferation assay.…”

Lymphoproliferative Responses to Recombinant HIV‐1 Envelope Antigens in Neonates and Infants Receiving gp120 Vaccines

“…High, intermediate, and low doses of vaccine antigen were chosen for evaluation, despite the fact that the low doses had previously proven inferior in adult studies in producing combined cellular and humoral immune responses. We chose to include the low dose because it was postulated that developmentally immature lymphocytes (e.g., cord blood at University of California, Santa Cruz on April 2, 2015 http://jid.oxfordjournals.org/ Downloaded from cells) respond to lower doses of antigen than do more functionally mature lymphocytes [4,5].…”

Ontogenic Development of Th1 and Th2 Cytokine Capabilities in Random Bred Mice

“…APC function has been reported to be immature in neonates (Clerici et al, 1993;Hunt et al, 1994;Trivedi et al, 1997). Yet others have reported an increased efficiency in neonatal APC function over those of adults (Van Tol et al, 1983;1984a,b;Marwitz et al, 1988). This inconsistency in reports of neonatal APC function caused us to approach this investigation from two directions.…”

“…Adult rather than contemporary APC were used as costimulators, a decision based on reports of neonatal APC immaturity. Although, some investigators contend that neonatal APC function is immature (Hunt et al, 1994), others report a 100-fold increase in efficiency over those of adults (Van Tol et al, 1983;1984a,b;Marwitz et al, 1988). Since lymphocytes and APC have evolved to function cooperatively, it is logical that function of one cell type at a specific age would be coordinated with that of the other cell type at the same age.…”