{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:30:53Z","timestamp":1778884253798,"version":"3.51.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"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":[[2001,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Numerous immunostimulatory protocols inhibit the development of T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse model. Many of these protocols, including treatment with the nonspecific immunostimulatory agents CFA or bacillus Calmette-Gue\u0301rin (BCG) vaccine, have been reported to mediate protection by skewing the pattern of cytokines produced by pancreatic \u03b2-cell autoreactive T cells from a Th1 (IFN-\u03b3) to a Th2 (IL-4 and IL-10) profile. However, most of these studies have documented associations between such cytokine shifts and disease protection rather than a cause\/effect relationship. To partially address this issue we produced NOD mice genetically deficient in IFN-\u03b3, IL-4, or IL-10. Elimination of any of these cytokines did not significantly alter the rate of spontaneous IDDM development. Additional experiments using these mice confirmed that CFA- or BCG-elicited diabetes protection is associated with a decreased IFN-\u03b3 to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but this is a secondary consequence rather than the cause of disease resistance. Unexpectedly, we also found that the ability of BCG and, to a lesser extent, CFA to inhibit IDDM development in standard NOD mice is actually dependent upon the presence of the Th1 cytokine, IFN-\u03b3. Collectively, our studies demonstrate that while Th1 and Th2 cytokine shifts may occur among \u03b2-cell autoreactive T cells of NOD mice protected from overt IDDM by various immunomodulatory therapies, it cannot automatically be assumed that this is the cause of their disease resistance.<\/jats:p>","DOI":"10.4049\/jimmunol.166.2.1352","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:56:47Z","timestamp":1398034607000},"page":"1352-1359","source":"Crossref","is-referenced-by-count":114,"title":["Th1 to Th2 Cytokine Shifts in Nonobese Diabetic Mice: Sometimes an Outcome, Rather Than the Cause, of Diabetes Resistance Elicited by Immunostimulation"],"prefix":"10.1093","volume":"166","author":[{"given":"David V","family":"Serreze","sequence":"first","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold D","family":"Chapman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina M","family":"Post","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellis A","family":"Johnson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilma L","family":"Suarez-Pinzon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta , Edmonton ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,1,15]]},"reference":[{"key":"2026020208113712200_R1","first-page":"71","volume-title":"NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer, and Other Diseases","year":"1998"},{"key":"2026020208113712200_R2","first-page":"613","volume-title":"Diabetes","year":"1994"},{"key":"2026020208113712200_R3","first-page":"291","volume-title":"Cell","year":"1996"},{"key":"2026020208113712200_R4","first-page":"291","volume-title":"Immunity","year":"1997"},{"key":"2026020208113712200_R5","first-page":"1579","volume-title":"J. 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