{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T03:10:44Z","timestamp":1770088244847,"version":"3.49.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we show that costimulation required for mucosal IgA responses is strikingly different from that needed for systemic responses, including serum IgA. Following oral immunization with cholera toxin (CT) adjuvant we found that whereas CTLA4-H\u03b31 transgenic mice largely failed to respond, CD28\u2212\/\u2212 mice developed near normal gut mucosal IgA responses but poor serum Ab responses. The local IgA response was functional in that strong antitoxic protection developed in CT-immunized CD28\u2212\/\u2212 mice. This was in spite of the fact that no germinal centers (GC) were observed in the Peyer\u2019s patches, spleen, or other peripheral lymph nodes. Moreover, significant somatic hypermutation was found in isolated IgA plasma cells from gut lamina propria of CD28\u2212\/\u2212 mice. Thus, differentiation to functional gut mucosal IgA responses against T cell-dependent Ags does not require signaling through CD28 and can be independent of GC formations and isotype-switching in Peyer\u2019s patches. By contrast, serum IgA responses, similar to IgG-responses, are dependent on GC and CD28. However, both local and systemic responses are impaired in CTLA4-H\u03b31 transgenic mice, indicating that mucosal IgA responses are dependent on the B7-family ligands, but require signaling via CTLA4 or more likely a third related receptor. Therefore, T-B cell interactions leading to mucosal as opposed to serum IgA responses are uniquely regulated and appear to represent separate events. Although CT is known to strongly up-regulate B7-molecules, we have demonstrated that it acts as a potent mucosal adjuvant in the absence of CD28, suggesting that alternative costimulatory pathways are involved.<\/jats:p>","DOI":"10.4049\/jimmunol.170.1.55","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:11:17Z","timestamp":1398125477000},"page":"55-63","source":"Crossref","is-referenced-by-count":43,"title":["Strong Differential Regulation of Serum and Mucosal IgA Responses as Revealed in CD28-Deficient Mice Using Cholera Toxin Adjuvant"],"prefix":"10.1093","volume":"170","author":[{"given":"Eva","family":"Ga\u0308rdby","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, University of Go\u0308teborg , Go\u0308teborg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Wrammert","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Lund , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Scho\u0308n","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, University of Go\u0308teborg , Go\u0308teborg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Ekman","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, University of Go\u0308teborg , Go\u0308teborg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Leanderson","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Lund , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Lycke","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, University of Go\u0308teborg , Go\u0308teborg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2026020210101126600_R1","first-page":"209","volume-title":"Chem. 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