A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity

Kate H. Gartlan, Gabrielle T. Belz, Jacqueline M. Tarrant, Gabriela Minigo, Maria Katsara, Kuo Ching Sheng, Mariam Sofi, Annemiek B. Van Spriel, Vasso Apostolopoulos, Magdalena Plebanski, Lorraine Robb, Mark D. Wright

Research output: Contribution to journalArticlepeer-review

Abstract

The cooperative nature of tetraspanin-tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. Previous functional studies of the tetraspanins CD37 and Tssc6 in the immune system found that both CD37 and Tssc6 regulate T cell proliferative responses in vitro. CD37-/- mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. In this study, we characterize "double knockout" mice (CD37 -/- Tssc6-/-) generated to investigate functional overlap between these tetraspanins. Strong evidence for a cooperative role for these two proteins was identified in cellular immunity, where both in vitro T cell proliferative responses and dendritic cell stimulation capacity are significantly exaggerated in CD37-/-Tssc6-/- mice when compared with single knockout counterparts. Despite these exaggerated cellular responses in vitro, CD37-/-Tssc6-/- mice are not more susceptible to autoimmune induction. However, in vivo responses to pathogens appear poor in CD37-/-Tssc6-/- mice, which showed a reduced ability to produce influenza-specific T cells and displayed a rapid onset hyper-parasitemia when infected with Plasmodium yoelii. Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37-/- or Tssc6-/- mice, demonstrating a complementary role for these two molecules in cellular immunity.

Original languageEnglish
Pages (from-to)3158-3166
Number of pages9
JournalJournal of Immunology
Volume185
Issue number6
DOIs
Publication statusPublished - 15 Sep 2010
Externally publishedYes

Fingerprint

Dive into the research topics of 'A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity'. Together they form a unique fingerprint.

Cite this