Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure

• Published in: Immunobiology (1979) 2016-01, Vol.221 (1), p.94-102
• Main Authors: Kim, Soochan, Han, Sinsuk, Lee, Ye Eun, Jung, Woong-Jae, Lee, Hyung Soo, Kim, Yong-Sun, Choi, Eun-Kyoung, Kim, Mi-Yeon
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; CD3 Complex - genetics; CD3 Complex - immunology; CD4 Antigens - genetics; CD4 Antigens - immunology; CD4 T cell; Chemokine CCL19 - genetics; Chemokine CCL19 - immunology; Chemokine CCL21 - genetics; Chemokine CCL21 - immunology; Chemokine CXCL13 - genetics; Chemokine CXCL13 - immunology; Gene Deletion; Gene Expression Regulation; LTi cell; Lymphocyte Count; Lymphotoxin-alpha - genetics; Lymphotoxin-alpha - immunology; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Prion; Prion Proteins; Prions - genetics; Prions - immunology; Prnp0/0; Receptors, CCR7 - genetics; Receptors, CCR7 - immunology; Receptors, CXCR5 - genetics; Receptors, CXCR5 - immunology; Receptors, Interleukin-7 - genetics; Receptors, Interleukin-7 - immunology; Signal Transduction; Spleen - immunology; Spleen - pathology; Spleen structure; Stromal Cells - cytology; Stromal Cells - immunology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - pathology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2015.07.017

Abstract The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient ( Prnp 0/0 ) Zürich I mice generated by inactivation of the Prnp gene. Prnp 0/0 mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp 0/0 mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3− CD4+ IL-7Rα+ LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells.