CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.
Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both C...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4596652?pdf=render |
| _version_ | 1818251325572382720 |
|---|---|
| author | Takeshi Kurihara Hideki Arimochi Zaied Ahmed Bhuyan Chieko Ishifune Hideki Tsumura Morihiro Ito Yasuhiko Ito Akiko Kitamura Yoichi Maekawa Koji Yasutomo |
| author_facet | Takeshi Kurihara Hideki Arimochi Zaied Ahmed Bhuyan Chieko Ishifune Hideki Tsumura Morihiro Ito Yasuhiko Ito Akiko Kitamura Yoichi Maekawa Koji Yasutomo |
| author_sort | Takeshi Kurihara |
| collection | DOAJ |
| description | Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders. |
| first_indexed | 2024-12-12T16:06:29Z |
| format | Article |
| id | doaj.art-ad6a671fdd9b4c6693ebf359c32eaf1f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T16:06:29Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ad6a671fdd9b4c6693ebf359c32eaf1f2022-12-22T00:19:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013969210.1371/journal.pone.0139692CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.Takeshi KuriharaHideki ArimochiZaied Ahmed BhuyanChieko IshifuneHideki TsumuraMorihiro ItoYasuhiko ItoAkiko KitamuraYoichi MaekawaKoji YasutomoUpon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders.http://europepmc.org/articles/PMC4596652?pdf=render |
| spellingShingle | Takeshi Kurihara Hideki Arimochi Zaied Ahmed Bhuyan Chieko Ishifune Hideki Tsumura Morihiro Ito Yasuhiko Ito Akiko Kitamura Yoichi Maekawa Koji Yasutomo CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. PLoS ONE |
| title | CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. |
| title_full | CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. |
| title_fullStr | CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. |
| title_full_unstemmed | CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. |
| title_short | CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo. |
| title_sort | cd98 heavy chain is a potent positive regulator of cd4 t cell proliferation and interferon γ production in vivo |
| url | http://europepmc.org/articles/PMC4596652?pdf=render |
| work_keys_str_mv | AT takeshikurihara cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT hidekiarimochi cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT zaiedahmedbhuyan cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT chiekoishifune cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT hidekitsumura cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT morihiroito cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT yasuhikoito cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT akikokitamura cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT yoichimaekawa cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo AT kojiyasutomo cd98heavychainisapotentpositiveregulatorofcd4tcellproliferationandinterferongproductioninvivo |