Immunologic abnormalities in HRS/J mice. I. Specific deficit in T lymphocyte helper function in a mutant mouse

Area of Science:

• Immunology
• Mouse models of disease
• T cell immunology

Background:

• The HRS/J mouse strain carries the 'hr' mutation, affecting hair growth and immune function.
• Previous studies suggest immune system abnormalities in HRS/J mice, but specific T cell defects require elucidation.

Purpose of the Study:

• To immunologically characterize T helper cell function in hr/hr homozygotes compared to hr/+ heterozygotes.
• To investigate the cellular basis of immune defects in HRS/J mice and their potential link to thymus abnormalities and leukemia.

Main Methods:

• Comparative immunologic analysis of spleen and lymph node cells from hr/hr and hr/+ mice.
• Assays for proliferative responses to alloantigens and mitogens.
• Assessment of cytotoxic effector cell generation in vitro.

Main Results:

• hr/hr spleen cells, unlike lymph node cells, demonstrated a specific defect in T helper cell-associated functions.
• This defect manifested as depressed proliferative responses to alloantigens.
• hr/hr spleen cells retained normal responsiveness to T cell mitogens and normal cytotoxic effector cell generation.

Conclusions:

• A specific defect in T helper cell function exists in hr/hr spleen cells, distinct from other immune cell functions.
• The defect is potentially linked to thymus epithelial abnormalities and high-level xenotropic virus expression in aged hr/hr thymocytes.
• These thymus abnormalities may contribute to the development of leukemia in this mouse model.