Murine neonatal CD4+ lymph node cells are highly deficient in the development of antigen-specific Th1 function in adoptive adult hosts

Becky Adkins, Yurong Bu, Patricia Guevara

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4998-5004
Number of pages7
JournalJournal of Immunology
Volume169
Issue number9
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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