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Modulation of lymphocyte function with inhibitory CD2: loss of NK and NKT cells

John R Ortaldo1, Anna Mason, Jami Willette-Brown

  • 1Laboratory of Experimental Immunology, Cancer and Inflammation Program, NCI-CCR, 560/31-93, Frederick, MD 21702-1201, USA.

Cellular Immunology
|November 28, 2007
PubMed

Insights

Altering CD2 molecule function in mice disrupted lymph node formation and impaired natural killer (NK) and NK T-cell development. These findings highlight CD2

Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • CD2 molecule's role in natural killer (NK) cell maturation is suggested but not fully understood.
  • Investigating CD2's function requires models that specifically alter its signaling pathways.

Purpose of the Study:

  • To investigate the role of CD2 signaling in NK cell maturation and lymphoid organ development.
  • To create and analyze a novel mouse model with an inhibitory CD2 molecule.

Main Methods:

  • Developed transgenic mice expressing an inhibitory CD2 molecule (CD2 Tg(ITIM)) on a CD2 knockout background.
  • Analyzed lymphoid organ morphology, including lymph nodes and thymus.
  • Assessed the frequencies and maturation of various lymphocyte populations (NK, NKT, T, and B cells) in peripheral organs.

Main Results:

  • Transgenic mice exhibited absent lymph nodes but normal thymus development.
  • Significant reduction in NK and NKT cell populations was observed in peripheral organs.
  • T and B cell frequencies remained intact, though functional defects and altered CD2 expression were noted.
  • NK cell maturation was impaired, with very low or absent CD2 expression on detected NK cells.

Conclusions:

  • The engineered inhibitory CD2 molecule significantly impacts lymphoid organogenesis and lymphocyte development.
  • These mice provide a valuable model for studying the intricate processes of lymphoid organ and lymphocyte development.
  • CD2 signaling is crucial for the proper development and maturation of NK and NKT cells.

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