CD44 Mediates Successful Interstitial Navigation by Killer T Cells and Enables Efficient Antitumor Immunity

Mrass P. et al. Immunity, 2008, 29: 971-985

Speaker: Jo-Shi Lin (林若曦)                   Time: 15:00-16:00, 4^th, Mar, 2009

Commentator: Dr. Pei-Jung Lu (呂佩融老師)      Place: 601

Abstract:

    Cytotoxic killer T lymphocytes (CTLs) are important immune cells against transformed tumor cells. CTLs migrate from the blood stream into organs, find their way through the extracellular matrix (ECM)-rich interstitial space, and finally interact physically with target cells. These steps,locomotion through tissue stroma and cell-cell interaction, are associated with cell polarity¹. Previously, the authors found that the tumor-infiltrating T lymphocytes (TILs) were in close contact with ECM fibers², which suggest that some adhesion molecules involve in the process. CD44 expressed on T lymphocytes is an adhesion molecule able to interact with blood vessel endothelium of activated T lymphocytes³. In this study, they further used CD44 deficiency OT-I T cell (OT-IxCD44^-/- CTL) to investigate whether CD44 involves in T cell migration in an intact tumor environment. They showed the OT-IxCD44^-/- CTL was not impaired in the differentiation, proliferation, and the cytotoxic activity. Under two-photon microscopy observation, however, the cell motility and cell polarity of OT-IxCD44^-/- CTL were impaired within an intact tumor environment. Furthermore, stable cell polarity was maintained by CD44, which intracellular domain interacts with the ezrin, radixin, moesin proteins. At the end, the authors demonstrated that the OT-IxCD44^-/- CTL was decreased in target cell screening and tumor rejecting activity. In conclusion, CD44 is a key regulator of the facultative polarity of killer T cell, which affects the cell navigation, and eventually destroy the target cell. 

References:

1.      Krummel M.F. et al. Maintenance and modulation of T cell polarity. Nat. Immunol. 2006, 7: 1143–1149.

2.      Mrass, P. et al. Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J. Exp. Med. 2006, 203: 2749-2761.

3.      DeGrendele H.C. et al. Requirement for CD44 in activated T cell extravasation into an inflammatory site. Science. 1997, 278: 672–675.