Sandeep K. Tripathy, M.D., Ph.D.

Assistant Professor
Internal Medicine

Immunology Program

  • 314-362-2162

  • 314-362-2308

  • 314-454-5108

  • 8124

  • 1021 Clinical Science Research Bldg. North Tower


  • innate immunity, NK cells, receptors, signal transduction, tolerance

  • Receptor-mediated modulation of NK cell responses in vivo

Research Abstract:

Natural killer (NK) cells are a cellular component of the innate immune system and act as a first line of defense against virus-infected or transformed cells. The expression of a varied repertoire of both activating and inhibitory receptors on the NK cell surface not only allows them to protect the host against pathogens but also prevents detrimental NK cell-mediated autoimmune responses. Ly49H is an activating receptor specifically expressed on NK cells in certain strains of mice that recognizes the murine cytomegalovirus (MCMV) encoded protein m157. This receptor has been shown to confer resistance to MCMV infection. We recently generated a transgenic mouse (m157-Tg) that expresses m157 under the control of the beta-actin promoter. We demonstrated that the continuous engagement of activating receptors on the NK cell results in decreased function (hyporesponsiveness) of the NK cell. Our results suggest, that although stimulation of the activating receptor is important for generating a robust NK cell immune response, stimulation through the same receptor can also result in NK cell hyporesponsiveness (NK cell tolerance). Currently, little is known about the factors controlling the different outcomes seen upon activating receptor engagement or in the mechanism(s) involved in mediating hyporesponsiveness (tolerance) of the NK cell following prolonged stimulation through an activating receptor. The m157-Tg mouse model provides a system to investigate not only the impact of persistent NK cell activation receptor stimulation on NK cell hyporesponsiveness (tolerance), but also the mechanism(s) and other associated factors involved in NK cell tolerance following prolonged stimulation through an activating receptor. Using our model system we are addressing the following questions:
(1) Determine the extent of the functional defects in tolerant NK cells.
(2) Evaluate the differences between a normal and tolerant NK cell that result in the phenotype observed.
(3) Determine the role of activating receptor signaling in the induction of NK cell tolerance.
(4) Elucidate activation receptor independent factors involved in the induction of NK cell tolerance.

Selected Publications:

Mazumdar, B, Bolanos F and Tripathy SK. Viral infection transiently reverses activation receptor-mediated NK cell hyporesponsiveness in an MHC class I-independent mechanism. Eur J Immunol. 2013: 43: 5: 1345-55.

Bolanos F and Tripathy SK. Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible. J Immunol. 2011: 185: 5: 2765-71.

Tripathy SK, Keyel PA, Yang L, Pingel JT, Cheng, T, Schneeberger, A and Yokoyama WM. Continuous engagement of a self-specific activation receptor induces NK cell tolerance. J Exp. Med. 2008 205: 8: 1829-41.

Tripathy SK, Smith HRC, Holroyd EA, Pingel JT and Yokoyama WM. Expression of m157, a murine cytomegalovirus-encoded putative major histocompatibility class I (MHC-I)-like protein, is independent of viral regulation of host MHC- I. J Virol. 2006 80: 1:545-50.

Tripathy SK, Svensson EC, Black HB, Goldwasser E, Margalith M, Hobart PM, and Leiden JM. Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector. Pro Natl Acad Sci. 1996 93: 10876-10880.

Tripathy SK, Black HB, Goldwasser E, Leiden JM. Immune response to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med. 1996 2: 545-550.

Tripathy SK, Goldwasser E, Lu MM, Barr E, and Leiden JM. Stable delivery of physiologic levels of recombinant erythropoietin to the systemic circulation by intramuscular injection of replication-defective adenovirus vectors. Pro Natl Acad Sci. 1994 91: 11557-11561.

Last Updated: 8/7/2013 2:17:42 PM

Back To Top

Follow us: