{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:13:29Z","timestamp":1791278009440,"version":"4.1.0"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,7,3]]},"abstract":"<jats:p>It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1\/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4+ subset (Th1 and Th2) responses but not CTL responses in vivo.<\/jats:p>","DOI":"10.1084\/jem.192.1.53","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"53-62","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["Inducible Costimulator Protein (Icos) Controls T Helper Cell Subset Polarization after Virus and Parasite Infection"],"prefix":"10.1084","volume":"192","author":[{"given":"Manfred","family":"Kopf","sequence":"first","affiliation":[{"name":"aBasel Institute for Immunology, 4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Coyle","sequence":"additional","affiliation":[{"name":"bDepartment of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schmitz","sequence":"additional","affiliation":[{"name":"aBasel Institute for Immunology, 4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Barner","sequence":"additional","affiliation":[{"name":"aBasel Institute for Immunology, 4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Oxenius","sequence":"additional","affiliation":[{"name":"cNuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awen","family":"Gallimore","sequence":"additional","affiliation":[{"name":"cNuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Carlos","family":"Gutierrez-Ramos","sequence":"additional","affiliation":[{"name":"bDepartment of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"aBasel Institute for Immunology, 4005 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,7,3]]},"reference":[{"key":"2023072509213724900_R1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1126\/science.7688139","article-title":"Differential T cell costimulatory requirements in CD28-deficient mice","volume":"261","author":"Shahinian","year":"1993","journal-title":"Science."},{"key":"2023072509213724900_R2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1074-7613(00)80308-8","article-title":"Duration of TCR stimulation determines costimulatory requirements","volume":"5","author":"K\u00fcndig","year":"1996","journal-title":"Immunity."},{"key":"2023072509213724900_R3","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.4049\/jimmunol.158.9.4082","article-title":"CD28 dependence of T cell differentiation to IL-4 production varies with the particular type 2 immune response J","volume":"158","author":"Gause","year":"1997","journal-title":"Immunol."},{"key":"2023072509213724900_R4","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1084\/jem.184.3.803","article-title":"Limited role of CD28-mediated signals in T helper subset differentiation","volume":"184","author":"Brown","year":"1996","journal-title":"J. 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