CD4+ TSCMs in the Bone Marrow Assist in Maturation of Antibodies against Influenza in Mice

• Published in: Mediators of inflammation 2019-01, Vol.2019 (2019), p.1-10
• Main Authors: Qiu, Li-Jun, Li, Yuqing, Guo, Guangwu, Wang, Fei, Wu, Kang, Li, Xuefeng
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral - immunology; Antigens; Ataxin-1 - metabolism; Bcl-2 protein; Bone marrow; Bone Marrow Cells - cytology; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - cytology; Cell division; Chemokine CXCL12 - metabolism; Cytokines; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Homeostasis; Immunoglobulins; Immunologic Memory; Immunological memory; Immunology; Immunotherapy; Infections; Infectious diseases; Influenza; Interleukin 15; Interleukin 7; Interleukin-15 - metabolism; Interleukin-2 Receptor beta Subunit - metabolism; Interleukin-7 - metabolism; Laboratory animals; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Memory cells; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - therapy; Proto-Oncogene Proteins c-bcl-2 - metabolism; Spleen; Stem cell transplantation; Stem cells; Stromal Cells; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - metabolism; Viruses
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2019/3231696

The bone marrow (BM) is not only a reservoir of hematopoietic stem cells but a repository of immunological memory cells. Further characterizing BM-resident memory T cells would be helpful to reveal the complicated relationship between the BM and immunological memory. In this study, we identified CD122high stem cell antigen-1 (Sca-1) high B cell lymphoma 2 (Bcl-2) high CD4+ stem cell-like memory T cells (TSCMs) as a distinct memory T cell subset, which preferentially reside in the BM, where they respond vigorously to blood-borne antigens. Interestingly, the natural CD4+ TSCMs homing to the BM colocalized with VCAM-1+ IL-15+ IL-7+ CXCL-12+ stromal cells. Furthermore, compared to spleen-resident CD4+ TSCMs, BM-resident TSCMs induced the production of high-affinity antibodies against influenza by B lymphocytes more efficiently. Taken together, these observations indicate that the BM provides an appropriate microenvironment for the survival of CD4+ TSCMs, which broadens our knowledge regarding the memory maintenance of antigen-specific CD4+ T lymphocytes.