Exclusive Th2 primary effector function in spleens but mixed Th1/Th2 function in lymph nodes of murine neonates

Recent studies have shown that neonatal mice are competent to develop matur e, Ag-specific Th1 function in situ, However, under many conditions, Th2 re sponses 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 prim ary Th1/Th2 effecters generated in situ in the spleens and lymph nodes. As assessed by the detection of IFN-gamma- or IL-4-producing cells, adults dev eloped mixed Th1/Th2 responses in both organs. Neonatal lymph nodes contain ed mature frequencies of IFN-gamma- and IL-4-producing cells. In striking c ontrast, while mature frequencies of Th2 cells developed in neonatal spleen s, virtually no IFN-gamma-secreting cells were detected. Exclusive Th2 func tion 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 ef fecters were virtually undetectable, the addition of rIL-12 boosted the fre quency of IFN-gamma-secreting cells to adult levels. Therefore, Th1 effecte rs apparently developed in situ, but Th1 effector function either was not p romoted or was inhibited upon subsequent exposure to the Ag in culture. Tog ether, these results indicate that the quality of a primary Th response in neonates is strongly dependent on the site of initial Ag exposure; response s initiated in the lymph nodes are mixed Th1/Th2, whereas responses occurri ng in the spleen are heavily Th2 biased.