Genetic defect in T lymphocyte-specific homing into peripheral lymph nodes

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Lymphocytes, including T cells and B cells, normally home to specific lymphoid tissues.
• Peripheral lymph nodes (PLN) are typically rich in T cells, while B cells are found in spleen and Peyer's patches (PP).
• DDD/1 mice exhibit an unusual scarcity of lymphocytes, particularly T cells, in their PLN.

Purpose of the Study:

• To investigate the cause of the T cell deficiency in the PLN of DDD/1 mice.
• To determine if the defect is due to lymphopenia or a specific homing abnormality.
• To identify the genetic basis and cellular mechanism of this T cell homing defect.

Main Methods:

• Immunohistochemistry to assess lymphocyte distribution in PLN.
• Analysis of lymphocyte content in peripheral blood, spleen, and PP.
• In vivo homing assays using fluorescence-labeled lymphocytes.
• Genetic analysis to identify the causative gene.
• Reciprocal bone marrow transplantation.
• Stamper-Woodruff adhesion assays.

Main Results:

• DDD/1 mice have significantly lower T cell frequencies in PLN (20-40%) compared to controls (60-80%).
• B cell colonization in PLN and lymphocyte content in PP were normal in DDD/1 mice.
• T cell content was higher in peripheral blood and spleen of DDD/1 mice.
• A single autosomal recessive gene, plt (paucity of lymph node T cells), was identified as responsible for the defect.
• Bone marrow transplantation suggested the defect originates in the PLN stroma, not lymphocytes.
• Homing assays confirmed a T cell-specific defect, occurring post-adhesion, as lymphocyte-endothelial binding and L-selectin/PNAd interactions were normal.

Conclusions:

• The plt gene in DDD/1 mice causes a T cell-specific homing defect into PLN.
• This defect is not due to lymphopenia but rather a disruption at a post-adhesion stage of homing.
• The plt locus product likely plays a critical role in T cell homing into PLN.