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CD44s is a negative regulator of IL‐2 mediated T‐cell proliferation
Author(s) -
Martinez Hunter,
Kaber Gernot,
Marshall Payton,
Barlow Graham,
Nagy Nadine,
Bollyky Paul
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03019
Subject(s) - microbiology and biotechnology , cd44 , cell growth , receptor , biology , cytokine , t cell , programmed cell death , cell , immunology , apoptosis , immune system , biochemistry
T lymphocytes receive co‐stimulatory and inhibitory signals from the extracellular matrix to regulate their proliferation but the underlying machinery of these interactions is unclear. T‐cell activation involves antigen recognition through a T cell receptor, the engagement of co‐stimulatory receptors and production of cytokines such as IL‐2. IL‐2 is a pleotropic cytokine which signals through the trimeric IL‐2 receptor complex leading to proliferation and differentiation. During T cell activation, the matrix receptor CD44 is upregulated. CD44 is primarily envisioned as a receptor involved in T lymphocyte trafficking through interactions with hyaluronan (HA), a ubiquitous component of the extracellular matrix. Herein, we observe the standard isoform of CD44 (CD44s) negatively influences proliferation of the IL‐2 dependent T cell line, CTLL‐2. CD44s exerts the influence on proliferation through an IL‐2‐pSTAT5 independent pathway. Furthermore, using an inducible system to control CD44s expression, strong induction of CD44s results in CTLL‐2 death through an unknown mechanism. Surprisingly, alternative splicing of CD44 variants (CD44v) which only differ in the extra‐cellular‐domain stalk region of the protein, rescues the death phenotype. These observations suggest CD44s may limit a T cell's response to IL‐2 through inhibition of an IL‐2 mediated growth pathway resulting in cell death and that CD44 alternative splicing relieves the inhibition.