Murine neonatal CD4+ lymph node cells are highly deficient in the development of antigen-specific Th1 function in adoptive adult hosts.
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.
Adkins
Becky
B
Department of Microbiology and Immunology, University of Miami Medical School, FL 33136, USA. radkins@med.miami.edu
Bu
Yurong
Y
Guevara
Patricia
P
D019264:Adoptive Transfer / Q000379:methods; D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005260:Female; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018984:Epitopes, T-Lymphocyte