The Primary Responses of Murine Neonatal Lymph Node CD4+ Cells are Th2-skewed and are Sufficient for the Development of Th2-biased Memory

Exposure of neonatal mice to antigen often results in Th2-biased responses in later life. Examples of this Th2 tendency are (a) secondary antibody responses dominated by the Th2-associated IgG1 isotype and (b) Th2-mediated tolerance to alloantigens. We previously reported that neonates develop primary Th1 and Th2 function in the lymph nodes but exclusive Th2 primary splenic responses. Here, we have tested whether the Th2 bias of adults initially immunized as neonates is due to the early, primary Th2 polarization in the spleen. Surprisingly, removal of the spleen at birth had no affect on either IgG1-dominant secondary responses or the development of tolerance to alloantigens. Thus, neonatal lymph nodes are sufficient to generate Th2-biased function following neonatal antigen exposure. To understand how this could arise, we examined the primary Th1/Th2 responses of CD4+ lymph node cells. Unlike the balanced Th1/Th2 responses seen with total lymph node cells, the primary responses of isolated CD4+ cells were skewed to IL-4 producing function. These results suggest that the early development of Th2-dominant responses by lymph node CD4+ cells contributes substantially to the subsequent development of Th2-dominant memory in neonates

Murine Neonatal CD4 +

It is well established that murine neonates are biased toward Th2 responses. Th2-dominant responses are observed following immunization with a variety of Ags, using different carrier/adjuvant systems, and are seen in both BALB/c and C57BL/6 mice. Therefore, Th2 skewing appears to be a universal phenomenon unique to the neonatal period. One important question about this phenomenon is whether these responses are due to T cell intrinsic properties or are regulated by the neonatal environment. Here we have addressed this issue by transferring neonatal or adult CD4(+) lymph node cells to adoptive adult recombinase-activating gene 2(-/-) hosts and studied the development of Th responses. Neonatal CD4(+) cells were highly deficient in the development of both primary and secondary Ag-specific Th1 responses. This did not appear to be due to anergy of a developed population, since exogenous IL-2 only marginally increased production of the Th1 cytokine IFN-gamma. This profound Th1 deficiency was observed despite similar proliferation by neonatal and adult cells within the recombinase-activating gene 2(-/-) hosts. Moreover, neonatal CD4(+) cells up-regulated activation markers in a manner similar to adult CD4(+) cells. Therefore, although their proliferation and phenotypic maturation proceeded normally, neonatal CD4(+) cells appeared to be intrinsically deficient in the functional maturation of Th1 lineage cells. These results offer a candidate explanation for the reduced graft-vs-host responses observed following transplantation of cord blood cells or murine neonatal lymphoid cells to allogeneic adult hosts

Murine Neonatal Lymphocytes Show Rapid Early Cell Cycle Entry and Cell Division

Neonatal animals are highly susceptible to infectious agents. At least part of this susceptibility is due to the virtual absence of immunological memory in newborns. One of the hallmarks of memory is the rapidity of the response. We show in this study that neonates may make up for their lack of memory, at least in part, by the rapid entry of large proportions of naive lymphocytes into the cell cycle. Following activation, greater percentages of both CD4(+) and CD8(+) neonatal, as compared with adult, lymph node cells showed early cell cycle entry; this was assessed by propidium iodide staining, CFSE labeling profiles, [(3)H]thymidine uptake, and up-regulation of early activation markers. This rapid cycle entry was observed following polyclonal activation with anti-CD3 or with PMA and ionomycin and in both C57BL/6 and BALB/c mice. Stimulation with specific peptide also elicited more rapid proliferative responses from neonatal vs adult TCR transgenic CD4(+) cells. In addition, more rapid cycle entry was observed in vivo, in lymphopenic RAG2(-/-) hosts. For both CD4(+) and CD8(+) cells, this phenomenon was observed out to 3 wk of life, although the differences between neonatal and adult cells became smaller with increasing time postbirth. These properties of peripheral neonatal T cells appeared to be inherited from their thymic precursors, because CD4(+)8(-) single-positive cells in the neonatal thymus also showed more rapid cycle entry, compared with their counterparts in the adult thymus. Interestingly, rapid early cycling was also observed among activated neonatal B cells, compared with adult B cells. Thus, early cell cycle entry by large proportions of cells may allow the naive lymphocyte population to efficiently mobilize responses against the broad range of pathogens first encountered in neonatal life

Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells

Neonatal and adult mice mount distinct responses to allogeneic cells. Injection of neonates with fully allogeneic cells results in lethal graft-vs.-host disease (GVHD), whereas injection of semi-allogeneic (F1) cells leads to lifelong tolerance to the alloantigens, often marked by specific CTL non-responsiveness. In contrast, adults injected with the same number of either cell type become primed and develop vigorous anti-donor CTL activity. One possibility for this differential responsiveness may be developmental immaturity in the CTL arm of the immune system. Recent studies have shown that neonates are capable of mounting mature CTL responses, but only in the presence of strong Th1-promoting agents. Here, we demonstrate that neonates are competent to develop vigorous MHC class I-restricted CTL activity in vivo upon exposure to either fully or semi-allogeneic spleen cells. Specific CTL activity was generated using doses of cells approximately tenfold lower than levels used for the induction of GVHD or tolerance. Thus, the present studies demonstrate that mouse neonates are fully mature in their capacity to develop alloreactive CTL activity, as long as the dose of donor cells is low enough. These results have important implications for the known exposure of human fetuses and infants to small numbers of maternal cells

Hierarchically porous biochar derived from aerobic granular sludge for high-performance membrane capacitive deionization

Membrane capacitive deionization (MCDI) is a cost-effective desalination technique known for its low energy consumption. The performance of MCDI cells relies on the properties of electrode materials. Activated carbon is the most widely used electrode material. However, the capacitive carbon available on the market is often expensive. Here, we developed hierarchically porous biochar by combining carbonization and activation processes, using easily acquired aerobic granular sludge (AGS) from biological sewage treatment plants as a precursor. The biochar had a specific surface area of 1822.07 m2 g−1, with a micropore area ratio of 58.65% and a micropore volume of 0.576 cm3 g−1. The MCDI cell employing the biochar as electrodes demonstrated a specific adsorption capacity of 34.35 mg g−1, comparable to commercially available activated carbon electrodes. Our study presents a green and sustainable approach for preparing highly efficient, hierarchically porous biochar from AGS, offering great potential for enhanced performance in MCDI applications