CD49b‐dependent establishment of T helper cell memory

Abstract

CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD49b and that CD49b-deficient or -blocked memory CD4 T-cell precursors fail to migrate from blood into the marrow of the bone, and they especially fail to transmigrate through sinusoidal endothelial cells of the BM. In the marrow, memory CD4 T cells and the precursors contact stromal cells expressing collagen II that are specific ligands for CD49b. Interestingly, memory CD4 T cells on day 117 of an immune response also dock on IL-7(+)/collagen XI(+) stromal cells, whereas memory precursors on day 12 do not. These results indicate that the collagen receptor CD49b is required for the migration of memory CD4 T-cell precursors into their survival niches of the bone marrow.

Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss

“…In support, it was reported that a2b1 is required for the migration and retention of effector/memory CD4 + T cells to the bone marrow (40). In fact, these cells were shown to reside near bone marrow stromal cells, which produce both collagen and IL-7 (40,41). In addition, IL-7 enhanced a2b1-mediated adhesion of human Th17 cells to collagen (Fig.…”

Nonclassical CD4+CD49b+ Regulatory T Cells as a Better Alternative to Conventional CD4+CD25+ T Cells To Dampen Arthritis Severity

“…Furthermore, CD103 expression could also be implicated in their suppressive function as its expression was shown to be responsible for the retention of Treg cells in inflamed tissue by interaction with its ligand E-cadherin (65,66). Finally, expression of the a 2 integrin CD49b itself could also be important for their function because it was demonstrated that this integrin is required for the migration of memory CD4 T cell precursors into their survival niches of the bone marrow (67). Because VLA-2 also binds Col II, expression of CD49b could provide Treg cells with particular homing, survival, or more potent suppressive function in the context of arthritis because Col II is expressed by the damaged cartilage.…”

Immunological memories of the bone marrow

“…A second signal required for efficient translocation of activated CD4 + T cells is integrin α2 (VLA‐2, CD49b) 59, 145, 146. CD4 + memory T cells stained for CD49b, and thus blocked for efficient use of VLA‐2, did not immigrate into the bone marrow in adoptive transfer experiments.…”

“…VLA‐2 can bind to collagens I, II, and XI,147, 148 and collagen XI is exclusively expressed in the bone marrow. While on day 12 of an intentional murine immune response, CD4 + T lymphocytes in the bone marrow docked onto stromal cells expressing collagen II, on day 117, CD4 + memory T cells of that immune response were docking on to stromal cells expressing collagen XI, suggesting that VLA‐2 may be an essential adhesion molecule for the memory T cells to find a niche in the bone marrow 145. This observation also suggests that the lifestyle of resident memory T cells of the bone marrow might be not so different from the lifestyle of memory plasma cells.…”

“…This observation also suggests that the lifestyle of resident memory T cells of the bone marrow might be not so different from the lifestyle of memory plasma cells. In murine bone marrow, memory CD4 + and CD8 + T lymphocytes are found in close association if not direct contact with stromal cells 59, 117, 137, 145. They are individually dispersed throughout the parenchyme 117.…”