Journal Article

Type II membrane protein CD69 regulates the formation of resting T-helper memory

Koseki, Haruhiko, Zehentmeier, Sandra, Hosokawa, Hiroyuki, Tumes, Damon J, Radbruch, Andreas, Tokoyoda, Koji, Nakayama, Toshinori, Hayashizaki, Koji, Shinoda, Kenta, Iwamura, Chiaki, Hanazawa, Asami

2012

Overview

Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adoptive Transfer / Animals / Antibodies / Antigens, CD / Antigens, CD - genetics / Antigens, CD - immunology / Antigens, CD - metabolism / Antigens, Differentiation, T-Lymphocyte / Antigens, Differentiation, T-Lymphocyte - genetics / Antigens, Differentiation, T-Lymphocyte - immunology / Antigens, Differentiation, T-Lymphocyte - metabolism / B-Lymphocytes / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Biological Sciences / Bone marrow / Bone Marrow - immunology / Bone Marrow - metabolism / Bone Marrow Cells / Bone Marrow Cells - immunology / Bone Marrow Cells - metabolism / CD4 antigen / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - transplantation / CD69 antigen / Cells / Endothelial cells / Female / Flow Cytometry / genetics / Green Fluorescent Proteins / Green Fluorescent Proteins - genetics / Green Fluorescent Proteins - metabolism / humoral immunity / Immune response / Immunity (humoral) / Immunization / immunologic memory / Immunologic Memory - immunology / Immunological memory / immunology / Lectins, C-Type / Lectins, C-Type - genetics / Lectins, C-Type - immunology / Lectins, C-Type - metabolism / Lymphocytes / Lymphocytes T / Male / Membrane proteins / Membrane Proteins - genetics / Membrane Proteins - immunology / Membrane Proteins - metabolism / Memory / Memory cells / metabolism / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Knockout / Mice, SCID / Mice, Transgenic / Microscopy, Confocal / niches / Pathogens / Plasma / Plasma cells / Proteins / Spleen / Stromal Cells / Stromal Cells - immunology / Stromal Cells - metabolism / T lymphocytes / T-Lymphocytes, Helper-Inducer / T-Lymphocytes, Helper-Inducer - immunology / T-Lymphocytes, Helper-Inducer - metabolism / transplantation