ICOS costimulation expands Th2 immunity by augmenting migration of lymphocytes to draining lymph nodes.
The T cell costimulatory molecule ICOS regulates Th2 effector function in allergic airway disease. Recently, several studies with ICOS(-/-) mice have also demonstrated a role for ICOS in Th2 differentiation. To determine the effects of ICOS on the early immune response, we investigated augmenting ICOS costimulation in a Th2-mediated immune response to Schistosoma mansoni Ags. We found that augmenting ICOS costimulation with B7RP-1-Fc increased the accumulation of T and B cells in the draining lymph nodes postimmunization. Interestingly, the increased numbers were due in part to increased migration of undivided Ag-specific TCR transgenic T cells and surprisingly B cells, as well as non-TCR transgenic T cells. B7RP-1-Fc also increased the levels of the chemokines CCL21 and CXCL13 in the draining lymph node, suggesting ICOS costimulation contributes to migration by direct or indirect effects on dendritic cells, stromal cells and high endothelial venules. Further, the effects of B7RP-1-Fc were not dependent on immunization. Our data support a model in which ICOS costimulation augments the pool of lymphocytes in the draining lymph nodes, leading to an increase in the frequency of potentially reactive T and B cells.
Tesciuba
Amanda G
AG
Department of Medicine, Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Shilling
Rebecca A
RA
Agarwal
Monica D
MD
Bandukwala
Hozefa S
HS
Clay
Bryan S
BS
Moore
Tamson V
TV
Weinstock
Joel V
JV
Welcher
Andrew A
AA
Sperling
Anne I
AI
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012550:Schistosoma mansoni / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D016207:Cytokines; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein