CD2 expression on murine intestinal intraepithelial lymphocytes is bimodal and defines proliferative capacity

N Van Houten1, P F Mixter, J Wolfe

  • 1Department of Medicine, University of Vermont College of Medicine, Burlington 05405.

Insights

CD2 molecule expression on intestinal lymphocytes impacts T cell activation. CD2- T cells, particularly TCR alpha beta + IEL, show hyporesponsiveness, indicating CD2 absence correlates with nonresponsiveness.

Area of Science:

  • Immunology
  • T cell biology
  • Lymphocyte research

Background:

  • CD2 molecule is crucial for T cell activation via the T cell receptor (TCR).
  • Intestinal intraepithelial lymphocytes (IEL) exhibit a unique bimodal CD2 expression pattern.
  • TCR alpha beta + IEL are equally divided into CD2- and CD2+ subsets, while TCR gamma delta + IEL are mostly CD2-.

Purpose of the Study:

  • To investigate the functional significance of CD2 expression on IEL subsets.
  • To determine the proliferative response of CD2- and CD2+ IEL to stimulation.
  • To compare IEL responsiveness with T cells from autoimmune lpr mice.

Main Methods:

  • Flow cytometry to analyze CD2 expression on IEL subsets (TCR alpha beta + and TCR gamma delta +).
  • In vitro stimulation assays using anti-CD3 mAb, PMA, and ionomycin to assess T cell proliferation.
  • Comparison of IEL responses with peripheral T cells from lpr mice.

Main Results:

  • CD2+ IEL subsets (both TCR alpha beta + and TCR gamma delta +) proliferated vigorously upon stimulation.
  • CD2- IEL subsets showed significantly reduced proliferative responses.
  • Activation of CD2- IEL with anti-CD3 mAb led to TCR gamma delta + IEL expansion, but not TCR alpha beta + IEL.
  • CD2- T cells from lpr mice also exhibited hyporesponsiveness.

Conclusions:

  • CD2 expression is critical for the co-stimulatory function in T cell activation within IEL populations.
  • The absence of CD2 on TCR alpha beta + IEL correlates with hyporesponsiveness, suggesting anergy.
  • These findings highlight the role of CD2 in T cell activation and have implications for understanding immune responses in the gut and autoimmune conditions.