Murine Neonatal CD4+ Lymph Node Cells Are Highly Deficient in the Development of Antigen-Specific Th1 Function in Adoptive Adult Hosts

Abstract

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-γ. 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.

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

“…6), is consistent with this idea. Moreover, we recently reported (Adkins et al, 2002) that intrinsic properties of neonatal T cells contribute to Th2-skewing in vivo; in adoptive adult hosts, neonatal lymph node CD4 þ cells were highly deficient in the development of Th1 function. How might these functional differences between neonatal and adult CD4…”

Induction of Protective Immunity to Listeria monocytogenes in Neonates

“…Newborns are especially prone to infections for which cell-mediated immunity is protective (1,3). Neonates and infants also have a reduced or suboptimal capacity to mount an effective cell-mediated immunity in response to most vaccines (1,(3)(4)(5). However, introducing a vaccine Ag into the cytoplasm of APCs induces a significant CD8 CTL response even in neonates (3,6,7).…”

“…However, introducing a vaccine Ag into the cytoplasm of APCs induces a significant CD8 CTL response even in neonates (3,6,7). Contrary to the induction of CTLs, Th1 (IFN-␥ producing) CD4 T cell responses have not only been difficult to induce in the neonate, but appear even more difficult to sustain (4,5,8,9).…”

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

“…Antibody responses in infants were thought to be dominated by IgM due to inadequate function of helper T cells, thus making the antigen-specific B cells unable to undergo isotype switching and hypermutations [24,25]. T cell responses induced by neonatal immunization are indeed lower than in adults [26,27] and development of neonatal CD4 + Th1 functions is severely impaired [28]. However, it has been demonstrated that significant IgG responses may be induced after immunization with protein antigens (reviewed in [23]), indicating that T cell help to promote isotype switch of B cells from IgM to IgG is present already in the neonatal period of life.…”