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To address the importance of the G-proteins G\u03b1<jats:sub>i2<\/jats:sub>and G\u03b1<jats:sub>i3<\/jats:sub>in thymocyte and T cell function, we developed several mouse models. G\u03b1<jats:sub>i2<\/jats:sub>deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1\/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus. In both models an abnormal distribution of memory and na\u00efve CD4 T cells occurred, and peripheral CD4 and CD8 T cells had reduced chemoattractant responses. The loss of G\u03b1<jats:sub>i3<\/jats:sub>had no discernable impact, however the lack of both G-proteins commencing at the DP stage caused a severe T cell phenotype. These mice lacked a thymic medullary region, exhibited thymocyte retention, had a peripheral T cell deficiency, and lacked T cell chemoattractant responses. Yet a noteworthy population of CD4<jats:sup>+<\/jats:sup>PD-1<jats:sup>+<\/jats:sup>CXCR5<jats:sup>+\/\u2212<\/jats:sup>cells resided in the spleen of these mice likely due to a loss of regulatory T cell function. Our results delineate a role for G\u03b1<jats:sub>i2<\/jats:sub>in early thymocyte development and for G\u03b1<jats:sub>i2\/3<\/jats:sub>in multiple aspects of T cell biology.<\/jats:p>","DOI":"10.1038\/s41598-017-04537-4","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T10:50:51Z","timestamp":1497869451000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Loss of G\u03b1i proteins impairs thymocyte development, disrupts T-cell trafficking, and leads to an expanded population of splenic CD4+PD-1+CXCR5+\/\u2212 T-cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Il-Young","family":"Hwang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Kehrl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"4537_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.bcp.2016.04.005","volume":"114","author":"JH Kehrl","year":"2016","unstructured":"Kehrl, J. 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