TY - JOUR
T1 - A role for thymic stromal lymphopoietin in CD4+ T cell development
AU - Al-Shami, Amin
AU - Spolski, Rosanne
AU - Kelly, John
AU - Fry, Terry
AU - Schwartzberg, Pamela L.
AU - Pandey, Akhilesh
AU - Mackall, Crystal L.
AU - Leonard, Warren J.
PY - 2004/7/19
Y1 - 2004/7/19
N2 - Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor α chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor γ chain, γc. We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, γc/ TSLPR double KO mice had a greater lymphoid defect than γcKO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in γcKO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into γcKO mice induced the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti-IL-7 antibodies were injected. Interestingly, TSLP preferentially stimulated the proliferation and survival of CD4+ single positive thymocytes and peripheral T cells in vitro. Additionally, CD4+ T cells from TSLPR KO mice expanded less efficiently than WT CD4+ T cells in irradiated hosts, and TSLP preferentially expanded CD4+ T cells both in vitro and in vivo. Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4+ T cells.
AB - Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor α chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor γ chain, γc. We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, γc/ TSLPR double KO mice had a greater lymphoid defect than γcKO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in γcKO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into γcKO mice induced the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti-IL-7 antibodies were injected. Interestingly, TSLP preferentially stimulated the proliferation and survival of CD4+ single positive thymocytes and peripheral T cells in vitro. Additionally, CD4+ T cells from TSLPR KO mice expanded less efficiently than WT CD4+ T cells in irradiated hosts, and TSLP preferentially expanded CD4+ T cells both in vitro and in vivo. Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4+ T cells.
KW - CD8 T cells
KW - IL-7
KW - Knockout mice
KW - SCID
KW - Thymocyte development
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U2 - 10.1084/jem.20031975
DO - 10.1084/jem.20031975
M3 - Article
C2 - 15263024
AN - SCOPUS:3242757478
SN - 0022-1007
VL - 200
SP - 159
EP - 168
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -