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Harvard Med. Sch

As seen in: The Journal of Immunology
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Articles by Harvard Med. Sch

Tight regulation of memory CD4 T cells limits immunopathology following chronic viral infection

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By Dan Barouch, Harvard Med. Sch
| The Journal of Immunology Verified
CD4 T cells are critical for the induction of adaptive immune responses. Surprisingly, we published a report showing that memory CD4 T cells could also mediate lethal immunopathology following chronic lymphocytic choriomeningitis virus (LCMV) infection. To interrogate whether naive or memory CD4 T cells can similarly mediate immune dysregulation, we transferred equal numbers of naive or memory virus-specific CD4 T cells into naive mice, and infected these with chronic LCMV.
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PD-1 inhibits the TCR signaling cascade by sequestering SHP-2 phosphatase, preventing its translocation to lipid rafts and facilitating Csk-mediated inhibitory phosphorylation of Lck.

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By Kankana Bardhan, Harvard Med. Sch, Jessica Weaver, Nikolaos Patsoukis
| The Journal of Immunology Verified
PD-1 inhibits T cell responses but the biochemical mechanisms are poorly understood. PD-1 cytoplasmic tail contains an ITIM and an ITSM motif. SHP-2 tyrosine phosphatase interacts with the ITSM and has a critical role in PD-1-mediated inhibition. Although phosphatases are considered negative regulators of activation, SHP-2 deficient T cells display impaired activation of MAPK in response to TCR/CD3 stimulation.
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