Biographical Sketch

Research

The focus of my laboratory is to understand the role of accessory molecules on the surface of T lymphocytes in modulating the T cells response to antigen, and how these proteins influence susceptibility to disease. T cell recognition of antigen occurs through the interaction of the T cell receptor with an antigen-MHC complex. However, accessory proteins play critical roles in modulating both the initial responses to antigen as well differentiation into phenotypically distinct effector cells.

The importance of CD28 in T cell activation has been well documented; however, the mechanism by which CD28 regulates T cells remains controversial. We are currently exploring the biochemical basis for CD28 function using gene knockin mice that express mutated forms of CD28. This approach allows us to determine the in vivo consequence of crippling specific signaling motifs in the tail of CD28. Excitingly, we have initiated a clinical trial to determine the effectiveness of a drug that inhibits CD28 as a therapy for asthma.

Recently we have focused on the signals that terminate T cell responses. Much as specific receptors regulate T cell activation, there are distinct pathways which inhibit T cell function and are important in the resolution of inflammation. Ongoing studies are exploring the mechanism by which these pathways function and their roles in ling disease.

Publications

1. Green, J., and Maisel, H. Lens fodrin binds actin and calmodulin. 1984. Curr. Eye Res. 12:1433-1440.

2. Green, J.M., Turka, L.A., June, C.H., and Thompson, C.B. CD28 and staphylococcal enterotoxin synergize to induce MHC independent T-cell proliferation. 1992. Cell. Immunol. 145:11-20

3. Mao, X., Green, J.M., Safer, B., Lindsten, T., Frederickson, R.M., Miyamoto, S., Sonenburg, N., and Thompson, C.B. Regulation of translation initiation factor gene expression during human T cell activation. 1992. J. Biol. Chem. 267(28):20444-20450

4. Nickoloff, B.J., Mitra, R.S., Lee, K., Turka, L.A., Green, J., Thompson, C., and Shimizu, Y. Discordant expression of CD28 ligands, BB-1 and B7 on keratinocytes in-vitro and psoriatic cells in-vivo. 1993. Am. J. Path. 142(4):1029-40

5. Nickoloff, B.J., Mitra, R.S., Green, J.M., Zheng, X-G, Shimizu, Y., Thompson, C.B., and Turka, L.A. Accessory cell function of keratinocytes for superantigens: dependence on LFA-1/ICAM-1 interactions. 1993. J. Immunol. 150(6):2148-59

6. Turka, L.A, Gratiot-Deans, J., Kiem, D., Bandukwala, R., Green, J.M., Strahler, J. and Hanash, S.M. Elevated PCNA levels in immature thymocytes: dissociation from cell cycle progression. 1993 J. Immunol. 150(7):2746-52

7. Samet, J.H., Burstin, H.R., Green, J.M., and Singer, D.E. Sociodemographic determinants in the hospitalization decision: evaluation of an emergency department interhospital transfer policy. 1993. Ann. Emerg. Med. 22(5):813-8

8. Nestle, F.O., Mitra, R.S., Green, J., Shimizu, Y., Thompson, C., Turka, L.A., Activated keratinocytes present bacterial-derived superantigens to T lymphocytes: relevance to psoriasis. 1994. J. Derm Science. 6:127-133.

9. Green, J.M., Zheng, X., Shimizu, Y., Thompson, C.B. and Turka, L.A. T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA-1 mediated events. 1994. Eur. J. Immunol. 24:265-272

10. Goodman, R.E., Nestle, F., Naidu, Y.M., Green, J.M., Thompson, C.B., Nickoloff, B.J. and Turka, L.A. Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not interferon-?. 1994. J. Immunol 152:5189-5198

11. Walunas, T.L., Lenschow, D.J., Bakker, C.Y., Linsley, P.S., Freeman, G.J., Green, J.M., Thompson, C.B. and Bluestone, J.A. CTLA-4 can function as a negative regulator of T cell activation. 1994. Immunity. 1:405-413

12. *Green, J.M., *Noel, P.J., Sperling, A.I., Walunas, T.L., Gray, G.S., Bluestone, J.A. and Thompson, C.B., Absence of B7-dependent costimulation in CD28-deficient mice. 1994. Immunity 1:501-508 (*co-first author)

13. *Sperling, A.I, *Green, J.M., Mosley, R.L., Smith. P.L., DiPaolo, R.J., Klein, J.R., Bluestone, J.A. and Thompson, C.B., CD43 is a murine costimulatory factor that functions independently of CD28. 1995. J. Exp. Med., 182:139-146. (*co-first author)

14. Kelleher, M.D., Abe, M.K., Chao, T., Jain, M., Green, J.M., Solway, J., Rosner, M.R. and Hershenson, M.B., Role of map kinase activation in bovine tracheal smooth muscle mitogenesis. 1995. Amer. J. Physiol. 268:L894-901.

15. Kim J.S., Rabe, K.F., Magnussen, H., Green, J.M., White, S.R., Migration and proliferation of guinea pig and human airway epithelial cells in response to tachykinins. 1995. Amer. J. Physiol., 269:L119-126

16. Ding, L., Green, J.M., Thompson, C.B. and Shevach, E.M. B7/CD28 dependent- and independent- pathways for induction of CD40 ligand (CD40L) expression. 1995. J. Immunol. 155:5124-5132

17. Noel, P.J., Boise, L.H., Green, J.M. and Thompson, C.B., CD28 costimulation is required to prevent cell death during the primary activation of T cells. 1996. J. Immunol. 157:636-642.

18. Green, J.M. and Thompson, C.B., Homotypic interactions mediated through LFA 1/ICAM-3 decrease the proliferative response of activated T cells. 1996. Cell. Immunol. 171:126-131

19. *Brown, D.R., *Green, J.M., Moskowitz, N.H., Davis, M., Thompson, C.B. and Reiner, S.L., Limited role for CD28-mediated signals in T helper subset differentiation. 1996. J. Exp. Med. 184:803-810 (*Co-first author)

20. Vella, A.T., Mitchell, T., Groth, B., Linsley, P.S., Green, J.M., Thompson, C.B., Kappler, J.W. and Marrack, P. CD28 engagement and proinflammatory cytokines contribute to T cell proliferation and survival in vivo. 1996. J. Immunol. 158:4714-4720

21. Thurman, E.C., Walker, J., Jayaraman, S., Manjunath, N., Ardman, B. and Green, J.M. Regulation of in vitro and in vivo T cell activation by CD43. 1998. Int. Immunol. 10:691-701

22. Walker, J and Green, J.M. Structural requirements for CD43 function. 1999. J. Immunol. 162:4109-4114

23. Holdorf, A.D., Green, J.M., Levine, S.D., Straus, D.B., Link, V., Changelian, P.S., Allen, P.A. and Shaw, A.S. 1999. Proline residues in CD28 and the SH3 domain of Lck are required for T cell costimulation. J. Exp. Med. 190:375-384

24. Green, J.M., Karpitskiy, V.S., Kimzey, S.L. and Shaw, A.S. 2000. Coordinate regulation of T cell activation by CD2 and CD28. J. Immunol. 164:3591-3595

25. Wang, W., Kimzey, S.L., Link, V.L. and Green, J.M., 2000. Identification and cloning of a CD43 associated serine/threonine kinase. Cell. Immunol. 205:34-39

26. Burr, J.S., Savage, N.D.L., Kimsey, S.L., Messah, G.E., Shaw, A.S., Arch, R.H. and Green, J.M., 2001. Cutting Edge: Distinct motifs within CD28 regulate T cell proliferation and induction of Bcl-XL. J. Immunol. 166:5331-5335

27. Burr, J., S., Kimzey, S.L., Randolph, D.R. and Green J.M. 2001 Differential regulation of airway inflammation and T helper cell development by CD28 and CTLA4. Amer. J. Resp. Cell. Mol. Biol. 24:563-568

28. Bromley, S.K., Iaboni, A., Davis, S.J., Whitty, A., Green, J.M., Shaw, A.S., Weiss, A. and Dustin, M.L., 2001. The immunological synapse and CD28-CD80 interactions. Nature Immunology. 2:1159-1166

29. Savage, N.D.L., Kimzey, S.L., Bromley, S.K., Johnson, K.G., Dustin, M.L. and Green, J.M., 2002. Polar redistribution of the sialoglycoprotein CD43, implications for T cell function. J. Immunol. 168:3740-3746

30. Kemper, C., Chan, A.C., Green, J.M., Brett, K.A., Murphy, K.M. and Atkinson, J.P., 2003 CD46/CD3 activation of human CD4+ cells induces a T-regulatory 1 (Tr1) phenotype. Nature 421:388-392

31. Beck, J. M., Blackmon, M.B., Rose, C.M., Kimzey, S.L., Preston, A.M. and Green, J.M., 2003. T cell costimulatory molecule function determines susceptibility to infection with Pneumocystis carinii in mice. J. Immunol. 171:1969-1977

32. Toennies, H.M., Green J.M. and Arch, R.H., 2003. Expression of CD30 and OX40 on T lymphocyte subsets is controlled by distinct regulatory mechanisms. J. Leuk. Biol., 75:350-357.

33. Kimzey, S.L., Liu, P. and Green, J.M. 2004 Requirement for CD28 in the effector phase of allergic airway inflammation. J. Immunol. 173:632-640

34. Rose, C.M., Kimzey, S.L. and Green, J.M. 2006. The host response of CD28-deficient mice to Pneumocystis infection. Microbial Pathogenesis 40:23-28

35. Deppong, C., Juehne, T.I., Hurchla, M., Friend, L.D., Shah, D.D., Rose, C.M., Bricker, T.L., Shornick, L.P., Crouch, E., Murphy, T.L., Holtzman, M.J., Murphy, K.M. and Green, J.M., 2006 Cutting Edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammation, J. Immunol. 176:3909-3103

36. Hernandez, J.D., Nguyen, J.T., Wang, W., Ardman, B, Green, J.M., Fukuda, M and Baum, L.G. 2006. Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death. J. Immunol. 177:5328-5336

37. Friend, L.D., Shah, D.D., Deppong, C., Lin, J., Bricker, T.L., Juehne, T.I., Rose, C.M. and Green, J.M. 2006. A dose dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant, J Exp Med. 203:2121-2133

38. Green, J.M. A loss at the bedside. 2007 Ann. Intern. Med. 147:588

39. Deppong, C., Degnan, J.M., Murphy, T.L., Murphy, K.M. and Green, J.M. 2008. B and T lymphocyte attenuator, (BTLA), regulates T cell survival in the lung. J. Immunol. 181:2973-2979

40. Dodson, L.F., Boomer, J.S., Deppong, C.M., Shah, D.D., Sim, J., Bricker, T.L., Russell, J.H. and Green, J.M., 2008 Targeted knockin mice expressing mutations of CD28 reveal an essential pathway for costimulation. Mol. Cell. Biol. In Revision

Book Chapters/Reviews

1. Green, J.M., Noel, P.J., Sperling, A.I., Walunas, T.L., Gray, G.S., Bluestone, J.A. and Thompson, C.B., Costimulaton through the CD28 receptor. 1995. Proceedings of the AAP. 107:41-46

2. Green, J.M. and Thompson, C.B., Modulation of T cell proliferative responses by accessory cell interactions. 1994. Immunol Res. 13:234-243.

3. Green, J.M., The B7/CD28/CTLA4 T cell activation pathway: Implications for inflammatory lung disease. 2000. Am J. Resp. Cell. Mol. Biol. 22:261-264

4. Holtzman, M.J., Green, J.M. S. Jayaraman and R.H. Arch, Regulation of T cell apoptosis. 2000 Apoptosis. 5:459-471

5. Arch, RH and Green, J.M. Costimulatory molecules in T cell activation and transplantation. 2004. In Immunobiology of Organ Transplantation, Wilkes, D.S. and Burlingham, W.J. Eds. Kluwer Academic/Plenum Publishers.

6. Green, J.M., End of life care in the intensive care unit. 2007 In The Washington Manual of Critical Care, Kollef, M.H., Bedient, T.J., Isakow, W and Witt, c.A., Eds. Lippincott, Williams & Wilkins Publishers