The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells.
We have addressed the role of the inducible costimulator (ICOS) in the development of T cell help for B cells and in the generation, survival and reactivation of memory CD4 T cells and B cells. We find that while T cell help for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS-KO) mice, the IFN-gamma response is little affected, indicating a defect in helper function that is unrelated to cytokine production. In addition, the ICOS-negative T cells do not accumulate in B cell follicles. Secondary (memory), but not primary, clonal proliferation of antigen-specific B cells is impaired in ICOS-KO mice, as is the generation of secondary antibody-secreting cells. Analysis of endogenous CD4 memory cells in ICOS-KO mice, using MHC class II tetramers, reveals normal primary clonal expansion, formation of memory clones and long-term (10 wk) survival of memory cells, but defective expansion upon reactivation in vivo. The data point to a role of ICOS in supporting secondary, memory and effector T cell responses, possibly by influencing cell survival. The data also highlight differences in ICOS dependency of endogenous T cell proliferation in vivo compared to that of adoptively transferred TCR-transgenic T cells.
Mahajan
Simmi
S
Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, King's Buildings, Edinburgh, UK.
Cervera
Ana
A
MacLeod
Megan
M
Fillatreau
Simon
S
Perona-Wright
Georgia
G
Meek
Stephen
S
Smith
Andrew
A
MacDonald
Andrew
A
Gray
David
D
D019264:Adoptive Transfer; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007150:Immunohistochemistry; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein