Title:
The lifestyle of memory CD4 T lymphocytes in the bone marrow

Koji Tokoyoda Ph.D
Assistant Professor, Department of Immunology, Graduate School of Medicine, Chiba University

Abstract:
Memory CD4 T cells are key to the immunological memory. In their absence, the generation of high-affinity memory B cells and memory plasma cells are impaired. Despite their eminent importance for the regulation of immune reactions and immunological memory, little is known about generation, maintenance and reactivation of memory CD4 T cells in body. While memory plasma cells have been shown to reside preferentially in the bone marrow (BM), we here demonstrate that memory CD4 T cells are also maintained in the BM, resting next to IL-7-expressing stromal cells. In the course of a systemic immune response, CD4 T cells relocate to the BM within 2 months after their generation, a process involving integrin a 2 and CD69. Antigen-specific memory CD4 T cells of the BM express Ly-6C at high level, unlike most splenic CD44 hi CD4 T cells. Upon the secondary challenge with the antigen in vivo , they rapidly express cytokines and CD40L and induce activated B cells to produce high-affinity antibodies, indicating their functional activity in vivo and marking them as professional memory CD4 T lymphocytes.

References:
1. Tokoyoda, K., Hauser, A.E., Nakayama, T, Radbruch, A. Organization of immunological memory by bone marrow stroma. Nat. Rev. Immunol. 10:193-200, 2010.

2. Tokoyoda, K., Zehentmeier, S., Radbruch, A. Organization and maintenance of immunological memory by stroma niches. Eur. J. Immunol. 39:2095-2099, 2009 .

3. Tokoyoda, K., Zehentmeier, S., Hegazy, A.N., Albrecht, I., Grun, J.R., L o hning, M., Radbruch, A. Professional memory CD4 + T lymphocytes preferentially reside and rest in the bone marrow.Immunity 30:721-730, 2009.

4. Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B.I., Nagasawa, T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity 20:707-718, 2004.