Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow

Speaker: Chang, Hsu-En (張許恩)                            Time: 14:10~15:10, May 19, 2010

Commentator: Shieh, Chi-Chang (謝奇璋老師)          Place: Room 601

Abstract:

        T helper cells are a sub-group of lymphocytes that plays an important role in establishing and maximizing the capabilities of the immune system. Part of their professional functions are activating and directing other immune cells, such as generation of high-affinity memory B cells and long-lived plasma cells, maintenance and secondary expansion of memory CD8⁺ T lymphocytes. Most of all, there’s a group of T helper cells called memory CD4⁺ T cells that have an extended lifespan and rapidly respond to antigen. It needs IL-7 for survival niche. Here, the authors showed a model of memory CD4⁺ T cells homing to bone marrow (bone marrow) and resting in the definition of proliferation and cytokine production. They also defined Ly-6C and CD44 as one of markers of memory CD4⁺ T cells. First they proved that memory CD4⁺ T cells relocate to bone marrow stroma by monitoring LCMV-specific CD4⁺CD44^hi T cells populations in the spleen, lymph node (LN) and bone marrow after immunization for more than 120 days. Then they proved that memory CD4⁺ T cells were resting in bone marrow by comparing transcriptome of memory CD4⁺ T cells in bone marrow and spleen with microarray chip and comparing BrdU uptake between bone marrow and spleen memory CD4⁺ T Cells. They defined Ly-6C as a marker of antigen-specific memory CD4⁺ T cells by flow cytometry. They then found out that homing of memory CD4⁺ T cells to bone marrow was blocked when treated with anti-integrin α2 neutralizing Fab fragment. And they saw that antigen-specific memory CD4⁺ T cells were colocalized with IL-7-expressing cells in bone marrow by confocal microscope. In the end, they proved that memory Ly6C^hi CD4⁺ T cells from bone marrow provided help for affinity maturation by flow cytometry. In summary, they proved that memory T helper cells reside in bone marrow as resting cells, but they can quickly react to antigenic challenges to provide professional immunological help to plasma cell.

References:

1.          Bone Marrow Is a Preferred Site for Homeostatic Proliferation of Memory CD8 T Cells. Todd C. Becker, et al., J. Immunol. 2005, 174: 1269-1273.

2.          Lifetime of plasma cells in the bone marrow. Manz et al., NATURE, VOL 388, 10 JULY 1997.

3.          Ly-6C Is a Marker of Memory CD8⁺ T Cells. Theresa L. et al., J. Immunol. 1995, 155: 1873-1883.