CD49b-dependent establishment of T helper cell memory.

Area of Science:

• Immunology
• Cell Biology
• Hematology

Background:

• CD4 T cells are vital for immunological memory.
• Professional memory CD4 T cells reside in the bone marrow (BM).
• Mechanisms for memory CD4 T cell establishment and maintenance in BM are unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms of memory CD4 T cell homing to the BM.
• To identify the role of CD49b in memory CD4 T cell precursor migration into the BM.

Main Methods:

• Flow cytometry to analyze CD49b expression on memory CD4 T cells.
• In vivo migration assays using CD49b-deficient or blocked T-cell precursors.
• Co-culture systems to study T cell-stromal cell interactions in the BM.

Main Results:

• Memory CD4 T cells express high levels of CD49b.
• CD49b deficiency or blockade impairs T-cell precursor migration into the BM.
• CD49b mediates transmigration through BM sinusoidal endothelial cells.
• Memory CD4 T cells and precursors interact with collagen II-expressing stromal cells.
• Differentiated memory CD4 T cells interact with IL-7(+)/collagen XI(+) stromal cells.

Conclusions:

• CD49b is essential for memory CD4 T-cell precursor homing to the bone marrow.
• CD49b facilitates migration into specific survival niches within the BM.
• Stromal cell interactions mediated by CD49b are critical for establishing immunological memory in the BM.