A role for thymic stromal lymphopoietin in CD4(+) T cell development.
Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor alpha chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor gamma chain, gamma(c). We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, gamma(c)/TSLPR double KO mice had a greater lymphoid defect than gamma(c) KO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in gamma(c) KO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into gamma(c) KO 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.
Al-Shami
Amin
A
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Spolski
Rosanne
R
Kelly
John
J
Fry
Terry
T
Schwartzberg
Pamela L
PL
Pandey
Akhilesh
A
Mackall
Crystal L
CL
Leonard
Warren J
WJ
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D015851:Interleukin-7 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008957:Models, Genetic; D010641:Phenotype; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013696:Temperature; D013950:Thymus Gland / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D000094632:Thymic Stromal Lymphopoietin
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D004396:Coloring Agents; D016207:Cytokines; D015851:Interleukin-7; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse