PLoS ONE (Jan 2012)

SH2D2A modulates T cell mediated protection to a B cell derived tumor in transgenic mice.

  • Tone Berge,
  • Ingrid Helene Bø Grønningsæter,
  • Kristina Berg Lorvik,
  • Greger Abrahamsen,
  • Stine Granum,
  • Vibeke Sundvold-Gjerstad,
  • Alexandre Corthay,
  • Bjarne Bogen,
  • Anne Spurkland

DOI
https://doi.org/10.1371/journal.pone.0048239
Journal volume & issue
Vol. 7, no. 10
p. e48239

Abstract

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BACKGROUND: T cell specific adapter protein (TSAd), encoded by the SH2D2A gene, modulates signaling downstream of the T cell receptor (TCR). Young, unchallenged SH2D2A-deficient C57BL/6 mice exhibit a relatively normal immune phenotype. To address whether SH2D2A regulates physiologic immune responses, SH2D2A-deficient TCR-transgenic BALB/c mice were generated. The transgenic TCR recognizes a myeloma-derived idiotypic (Id) peptide in the context of the major histocompatibility complex (MHC) class II molecule I-E(d), and confers T cell mediated resistance to transplanted multiple myeloma development in vivo. PRINCIPAL FINDINGS: The immune phenotype of SH2D2A-deficient C57BL/6 and BALB/c mice did not reveal major differences compared to the corresponding wild type mice. When challenged with myeloma cells, Id-specific TCR-transgenic BALB/c mice lacking SH2D2A displayed increased resistance towards tumor development. Tumor free TCR-transgenic SH2D2A-deficient mice had higher numbers of Id-specific single positive CD4+ thymocytes compared to TCR-transgenic wild-type mice. CONCLUSION: Our results suggest a modulatory role for SH2D2A in T cell mediated immune surveillance of cancer. However, it remains to be established whether its effect is T-cell intrinsic. Further studies are required to determine whether targeting SH2D2A function in T cells may be a potential adjuvant in cancer immunotherapy.