TY - JOUR
T1 - The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function
AU - Wang, Jing
AU - Foster, Amy
AU - Chin, Robert
AU - Yu, Ping
AU - Sun, Yonglian
AU - Wang, Yang
AU - Pfeffer, Klaus
AU - Fu, Yang Xin
PY - 2002
Y1 - 2002
N2 - Highly organized lymphoid structures provide the intricate microenvironment essential for the mediation of the effective immune responses. Compared with lymphotoxin β knockout mice (LTβ-/-), LTβ receptor knockout (LTβR-/-) mice present with more severely disorganized splenic structures, suggesting the potential involvement of another ligand. LIGHT, a newly identified TNF family member, is a costimulatory molecule for T cells and binds to LTβR and herpes virus entry mediator (HVEM) in vitro. Here, we show that the complementation of LTα-/- mice with a LIGHT transgene (LIGHT Tg/LTα-/-) leads to the restoration of secondary lymphoid tissue chemokine and T/B cell zone segregation. LIGHT Tg/LTα-/- mice also preserve dendritic cells, follicular dendritic cell networks, and germinal centers, though not the marginal zone. Consequently, IgG responses to soluble, but not particulate, antigens are restored, confirming the role of primary follicle and marginal zone in the responses to soluble and particulate antigens. The failure of the LIGHT transgene to rescue the defective splenic structures in LTβR-/- mice demonstrates that LIGHT can interact with LTβR in vivo. More severely disorganized splenic structures developed after blockade of endogenous LIGHT in LTβ-/- mice. These findings uncover the potential interaction between LIGHT and one of its receptors, LTβR, in supporting even in the absence of LT the development and maintenance of lymphoid microenvironment.
AB - Highly organized lymphoid structures provide the intricate microenvironment essential for the mediation of the effective immune responses. Compared with lymphotoxin β knockout mice (LTβ-/-), LTβ receptor knockout (LTβR-/-) mice present with more severely disorganized splenic structures, suggesting the potential involvement of another ligand. LIGHT, a newly identified TNF family member, is a costimulatory molecule for T cells and binds to LTβR and herpes virus entry mediator (HVEM) in vitro. Here, we show that the complementation of LTα-/- mice with a LIGHT transgene (LIGHT Tg/LTα-/-) leads to the restoration of secondary lymphoid tissue chemokine and T/B cell zone segregation. LIGHT Tg/LTα-/- mice also preserve dendritic cells, follicular dendritic cell networks, and germinal centers, though not the marginal zone. Consequently, IgG responses to soluble, but not particulate, antigens are restored, confirming the role of primary follicle and marginal zone in the responses to soluble and particulate antigens. The failure of the LIGHT transgene to rescue the defective splenic structures in LTβR-/- mice demonstrates that LIGHT can interact with LTβR in vivo. More severely disorganized splenic structures developed after blockade of endogenous LIGHT in LTβ-/- mice. These findings uncover the potential interaction between LIGHT and one of its receptors, LTβR, in supporting even in the absence of LT the development and maintenance of lymphoid microenvironment.
KW - Antibody response
KW - Chemokine
KW - LIGHT
KW - LT β receptor
KW - Splenic structure
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U2 - 10.1002/1521-4141(200207)32:7<1969::AID-IMMU1969>3.0.CO;2-M
DO - 10.1002/1521-4141(200207)32:7<1969::AID-IMMU1969>3.0.CO;2-M
M3 - Article
C2 - 12115617
AN - SCOPUS:0036318880
SN - 0014-2980
VL - 32
SP - 1969
EP - 1979
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -