Specific CD45 isoforms differentially regulate T cell receptor signaling.

D Chui; C J Ong; P Johnson; H S Teh; J D Marth

doi:10.1002/j.1460-2075.1994.tb06322.x

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Specific CD45 isoforms differentially regulate T cell receptor signaling.

D Chui·C J Ong·P Johnson·H S Teh·J D Marth

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Abstract

Multiple isoforms of T cell CD45 tyrosine phosphatase are expressed as a result of alternative RNA splicing among extracellular exons. To discern the presence and identity of distinct functions among CD45 isoforms, we compared thymic T cell activation responses by elevating expression of two CD45 isoforms normally found on quiescent T cells. We report that CD45RABC significantly increased CD4+ thymic T cell proliferation in both a mixed lymphocyte reaction and following anti-T cell receptor (TCR) antibody stimulation. Additionally, CD45RABC enhanced Ca2+ mobilization and phosphotyrosine accumulation, and suppressed the inhibitory effect of anti-CD4 antibodies. By contrast, CD45R0 did not enhance TCR signaling or phosphotyrosine levels in CD4+ thymic T cells and required a TCR co-stimulus to augment cellular proliferation. These studies provide genetic evidence that alternative CD45 isoforms are functionally distinct and disclose a unique mechanism by which T cell immunologic responsiveness can be modified.

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Animals Antibodies CD4 Antigens Calcium Isoenzymes Lymphocyte Activation Mice Mice, Transgenic Phosphotyrosine Protein Tyrosine Phosphatases Receptors, Antigen, T-Cell Signal Transduction T-Lymphocytes Tyrosine Journal Article Research Support, Non-U.S. Gov't

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D Chui, C J Ong, P Johnson, H S Teh, J D Marth. 1994-02-15. Specific CD45 isoforms differentially regulate T cell receptor signaling.. https://doi.org/10.1002/j.1460-2075.1994.tb06322.x

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