Exclusive Th2 Primary Effector Function in Spleens but Mixed Th1/Th2 Function in Lymph Nodes of Murine Neonates

Abstract

Recent studies have shown that neonatal mice are competent to develop mature, Ag-specific Th1 function in situ. However, under many conditions, Th2 responses dominate in the neonate, while Th1 responses are more prevalent in adults. To compare further the immune responses of neonates and adults, we used the enzyme-linked immunospot method to measure the frequencies of primary Th1/Th2 effectors generated in situ in the spleens and lymph nodes. As assessed by the detection of IFN-gamma- or IL-4-producing cells, adults developed mixed Th1/Th2 responses in both organs. Neonatal lymph nodes contained mature frequencies of IFN-gamma- and IL-4-producing cells. In striking contrast, while mature frequencies of Th2 cells developed in neonatal spleens, virtually no IFN-gamma-secreting cells were detected. Exclusive Th2 function was observed in both BALB/c and C57BL/6 neonates, strains in which the Th2 and Th1 lineages, respectively, are favored in adults. Although Th1 effectors were virtually undetectable, the addition of rIL-12 boosted the frequency of IFN-gamma-secreting cells to adult levels. Therefore, Th1 effectors apparently developed in situ, but Th1 effector function either was not promoted or was inhibited upon subsequent exposure to the Ag in culture. Together, these results indicate that the quality of a primary Th response in neonates is strongly dependent on the site of initial Ag exposure; responses initiated in the lymph nodes are mixed Th1/Th2, whereas responses occurring in the spleen are heavily Th2 biased.

The key regulators of adult T helper cell responses, STAT6 and T‐bet, are established in early life in mice

“…Day 1 neonatal and adult WT or STAT6-deficient mice were immunized with DNP-KLH, and their antigenspecific IFN-c responses were tested in vitro 1 week later. As previously demonstrated [31], both the frequencies of IFN-c-secreting cells (Fig. 7a) and the levels of antigen-specific IFN-c production (Fig.…”

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

“…Differences are known to exist in the ontogenic development of spleen and lymph nodes (25,26) and it has been suggested that the kinetics of immune maturation may be more rapid in murine lymph nodes than in spleen (27). Therefore, the appearance of mature FDC clusters was also studied in cervical, submedullary, axillary, brachillary, inguinal, and mesenteric lymph nodes.…”

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

“…The culture conditions and the methods for assaying cytokine production by or cytokine secreting cells among total lymph node and spleen cells in response to restimulation with KLH have been previously described in detail (Adkins and Du, 1998;Adkins et al, 2000;Adkins et al, 2001).…”

“…Red cells were removed from spleen cell suspensions by hypotonic lysis and mesenteric, inguinal, axillary, brachial and cervical lymph nodes were pooled to prepare lymph node cell suspensions (Adkins and Du, 1998;Adkins et al, 2000). Preparations of spleen and lymph node cells were mixed and washed twice with HBSS prior to injection.…”