TY - JOUR
T1 - Neonatal exposure to antigen induces a defective CD40 ligand expression that undermines both IL-12 production by APC and IL-2 receptor up-regulation on splenic T cells and perpetuates IFN-γ-dependent T cell anergy
AU - Min, B.
AU - Legge, K. L.
AU - Bell, J. J.
AU - Gregg, R. K.
AU - Li, L.
AU - Caprio, J. C.
AU - Zaghouani, H.
PY - 2001/5/1
Y1 - 2001/5/1
N2 - T cell deletion and/or inactivation were considered the leading mechanisms for neonatal tolerance. However, recent investigations have indicated that immunity develops at the neonatal stage but evolves to guide later T cell responses to display defective and/or biased effector functions. Although neonatal-induced T cell modulation provides a useful approach to suppress autoimmunity, the mechanism underlying the biased function of the T cells remains unclear. In prior studies, we found that exposure of newborn mice to Ig-PLP1, a chimera expressing the encephalitogenic proteolipid protein (PLP) sequence 139-151, induced deviated Th2 lymph node cells producing IL-4 instead of IL-2 and anergic splenic T cells that failed to proliferate or produce IFN-γ yet secreted significant amounts of IL-2. However, if assisted with IFN-γ or IL-12, these anergic splenic T cells regained full responsiveness. The consequence of such biased/defective T cells responses was protection of the mice against experimental allergic encephalomyelitis. In this study, investigations were performed to delineate the mechanism underlying the novel form of IFN-γ-dependent splenic anergy. Our findings indicate that CD40 ligand expression on these splenic T cells is defective, leading to noneffective cooperation between T lymphocytes and APCs and a lack of IL-12 production. More striking, this cellular system revealed a requirement for IL-2R expression for CD40 ligand-initiated, IL-12-driven progression of T cells into IFN-γ production.
AB - T cell deletion and/or inactivation were considered the leading mechanisms for neonatal tolerance. However, recent investigations have indicated that immunity develops at the neonatal stage but evolves to guide later T cell responses to display defective and/or biased effector functions. Although neonatal-induced T cell modulation provides a useful approach to suppress autoimmunity, the mechanism underlying the biased function of the T cells remains unclear. In prior studies, we found that exposure of newborn mice to Ig-PLP1, a chimera expressing the encephalitogenic proteolipid protein (PLP) sequence 139-151, induced deviated Th2 lymph node cells producing IL-4 instead of IL-2 and anergic splenic T cells that failed to proliferate or produce IFN-γ yet secreted significant amounts of IL-2. However, if assisted with IFN-γ or IL-12, these anergic splenic T cells regained full responsiveness. The consequence of such biased/defective T cells responses was protection of the mice against experimental allergic encephalomyelitis. In this study, investigations were performed to delineate the mechanism underlying the novel form of IFN-γ-dependent splenic anergy. Our findings indicate that CD40 ligand expression on these splenic T cells is defective, leading to noneffective cooperation between T lymphocytes and APCs and a lack of IL-12 production. More striking, this cellular system revealed a requirement for IL-2R expression for CD40 ligand-initiated, IL-12-driven progression of T cells into IFN-γ production.
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U2 - 10.4049/jimmunol.166.9.5594
DO - 10.4049/jimmunol.166.9.5594
M3 - Article
C2 - 11313399
AN - SCOPUS:0035339860
SN - 0022-1767
VL - 166
SP - 5594
EP - 5603
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -