2002 - Permanent Member of NIH Study Section , Immunological Sciences (IMS)

NIH Reviewer, ad hoc for: NIH, Special Emphasis Panel ZRG1 SSS-J 01 R , Dec 4, 2001; NIH, Special Emphasis Panel “Sex-Based Differences in the Immune Response” , RFA AI- 01-005, November 7-8, 2001; NIH, Metabolism Study Section, Council MET, October 25-26, 2001; NIH, Council ZRG1 SS-T 10 B, July 09, 2001; NIH, Immunological Sciences Study Section, June 21-22, 2001; NIH NIAID “Innovation grants on Immune Tolerance” Special Emphasis Panel, Council Za/1 NN-1 M1, 02/08/01; NIH , SBIR grants ZRG1 SSS-T 10B, 11-13-200; NIH, Experimental Immunology Study Section, Nov. 29., 1999; NIH, Immunological Sciences Study Section, Feb 1999; NIH NAIAD Autoimmunity Centers of Excellence Reviewer, June 28, 1999; NIH HLBI, Special Emphasis Panel on “Immunogenetics of Inhibitor Formation in Hemophilia” June 1996; NIH NIAID Program Project Grant Review and site visit: PI: H. McDevitt “HLA-transgenic NOD mice”, July 22 -24,1998

1996– 2001: Associate Editor, The Journal of Immunology, regular reviewer for:, Biotechnology, The Journal of Immunology, Nephritis Dialysis Transplantation, The Journal of Clinical Investigation, Life Sciences, Nature Medicine, American J. Pathology, International Immunology, Journal of Experimental Medicine, Autoimmunity, Journal of Neuroimmunology, Immunity, Journal of Virology

Lehmann, P.V., Schumm, G., Moon, D., Hurtenbach, U., Falcioni, F., Muller, S., and Z.A. Nagy. 1990. Acute lethal graft-versus-host reaction induced by major histocompatibility complex class II-reactive T helper cell clones. J.Exp.Med. 171:1485-1496.

Falcioni, F, Dembic, Z., Muller, S., Lehmann, P.V., and Nagy, Z.A. 1990. Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin. J. Exp. Med. 171:1665-1681.

Tary-Lehmann, M., Rolink, A. G., Lehmann, P.V., Nagy, Z. A., and Hurtenbach, U. 1990. Induction of graft-versus-host-associated immunodeficiency by CD4 + T cell clones. J. Immunol. 145 : 2092-2098.

Lehmann, P.V ., Drexler, K., Tary-Lehmann, M., Falcioni, F., Hurtenbach, U., and Nagy, Z.A. 1991. Graft-versus-host resistancef by class II MHC-specific T cell clones. J. Exp. Med . 173:333-341.

Lehmann, P.V ., Forsthuber, T., Miller, A., and Sercarz, E.E. 1992. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358: 155-157.

Lehmann, P.V. , Sercarz, E.E., Forsthuber, T., Dayan, C.M. and Gammon, G. 1993. Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunology Today. 14:203-208.

Sercarz, E.E., Lehmann, P.V., Ametani, A., Benichou, G., Miller, A., and Moudgil, K. 1993. Dominance and crypticity of T cell antigenic determinants. Annual Review of Immunology . 11: 729-766.

Kaufman, D.L., Clare-Salzer, M. Tian, J., Forsthuber, T., Ting, G.S.P., Robinson, P., Atkinson, M.A., Sercarz, E.E., Tobin, A.J., and Lehmann, P.V. 1993. Spontaneous loss of T-cell tolerance to glutamate decarboxylase in murine insulin-dependent diabetes. Nature . 366: 69-72.

Ransohoff, R., Tuohy, V., and Lehmann, P.V. 1994. The Immunology of multiple sclerosis: new intricacies and new insights. Current Opinion in Neurology. 7:242-249.

Bhardwaj, V., Kumar, V., Grewal, I.S., Dao, T., Lehmann, P.V., Geysen, M. and Sercarz, E. 1994. The T cell determinat structure of myelin basic protein in B10.PL, SJL and their F1s. J. Immunol . 152:3711-9.

Benichou, G., Fedoseyeva, E., Lehmann, P.V., Olson, C.A., Geysen, M., McMillan, M., and Sercarz, E.E. 1994. Limited T cell response to donor MHC peptides and prevention of allograft rejection. J. Immunol . 153: 938-945.

Tary-Lehmann, M., Lehmann, P.V., Schols, D., Roncarolo, M.G. and Saxon, A. 1994. Anti-SCID mouse reactivity shapes the T cell repertoire in hu-PBL-SCID chimeras. J. Exp Med. 180: 1817-1827.

Tian, J., Lehmann, P.V. and Kaufman, D.L. 1994. T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility alleles. J. Exp Med . 180: 1979-1984.

Tary-Lehmann, M., Saxon, A., Lehmann, P.V. 1995. The human immune system in hu-PBL-SCID mice. Immunology Today , 16:529-533.

Forsthuber, T., Cheng, H., Lehmann, P.V. 1996. Induction of immunity in neonatal mice. Science . 271:1728-1730.

Tian, J., Atkinson, M. A., Clare-Salzler, M., Herschenfeld, A., Forsthuber, T., Lehmann, P.V., Kaufman, D. L. 1996. Induction of Th2 responses to glutamate decarboxylase (GAD65) by the nasal administration of GAD65 peptides prevents insulin-dependent diabetes. J. Exp Med . 183: 1561-1567.

Rudick, R. A., Ransohoff, R. M., Peppler, R., Medendorp, S. V., Lehmann, P. V., Alam, J. 1996. Interferon beta induces interleukin-10 expression: Relevance to multiple sclerosis. Annals of Neurology . 40: 618-627.

Tian, J., Clare-Salzler, M., Herschenfeld, A., Middleton, B., Newman, D., Evans, C., Atkinson, M., Mueller, R., Mullen, Y., Sarvetnick, N., Tobin, A. J., Lehmann, P. V., Kaufman, D. L. 1996. Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes prone mice. Nature Medicine. 2:1348-1353.

Lehmann, P. V., Heeger, P. 1997. Induction of Th1 or Th2 immunity to immunodominant indirect pathway peptide. Transplantation . 64:292-296.

Chu, R. S., Targoni, O. S., Kreig, A. M., Lehmann, P.V., Harding, C. V. 1997. CpG Oligodeoxynucleotides provide a danger signal and act as adjuvants that switch on Th1 immunity. J. Exp Med . 186:1623-1631.

Kaufman, D. L., Lehmann P. V., Tian, T. 1997. Determinant spreading of T helper-2 (Th2) responses to pancreatic auto-antigens. J. Exp Med . 186: 2039-2044.

Targoni, O. S., Lehmann, P.V. 1998. The MBP-specific T cell repertoire in MBP +/+vs. MBP -/- mice. J.Exp.Med 187 :2055-2065.

Matesic, D., Lehmann, P. V., Heeger, P. S. 1998. High resolution characterization of cytokine-producing alloreactivity in naive and allograft-primed mice. Transplantation. 65:906-914.

Lehmann, P. V ., Targoni, O. S., Forsthuber, T. G. 1998. Shifting T-cell activation thresholds in autoimmunity and determinant spreading. Immunol. Rev. 164:53-61.

Lehmann, P.V . 1998. The fate of T cells in the brain: veni, vidi, vici and veni, mori. Amer. J. Pathol. 153 :677-680.

Birnbaum, G., Kotilnek, L., Miller, D. S., Raine, C. S., Gao, Y. L., Lehmann, P. V., Gupta, R. S. 1998. Heat shock protein in experimental allergic encephalomyelitis. J. Neuroimmunal . 90(2):149-61.

Targoni, O. S., Tary-Lehmann, M., Lehmann, P. V. 1999. Prevention of murine EAE by hydrolytic enzyme treatment. J. Autoimmun . 12 :191-198.

Yip, H. C., Karulin, A. Y., Tary-Lehmann, M., Heeger, P., Trezza, R. T., Heinzel, F. P., Forsthuber, T., Lehmann, P. V. 1999. Adjuvant guided type 1 and type 2 immunity: infectious/non-infectious dichotomy defines the class of response. J. Immunol. 162: 3942-3949.

Karulin, A. Y., Hesse, M., Tary-Lehmann, M., Lehmann, P. V. 2000. Single cytokien producing CD4 memory cells prevail in vivo, in type1/type 2 immunity. J. Immunol . 164:1862-1872.

Helms, T., Boehm, B.O., Assad, R., Trezza, R. T., Lehmann, P. V., Tary-Lehmann, M. 2000. Direct visualization of cytokine-producing recall-antigen-specific CD4 memory T cells in healthy individuals and HIV patients. J. Immunol . 164: 3723-3732.

Heeger, P. S., Forsthuber, T., Shive, C., Beikert, E., Genain, C. P., Hofstetter, H., Karulin, A., Lehmann, P. V. 2000. Revisiting tolerance induced by autoantigen in incomplete Freund's adjuvant. J. Immunol . 164: 5771-5781.

Heeger, P.S., Valujskih,A., Lehmann, P.V. 2000.Comprehensive assessment of determinant specificity, frequency, and cytokine signature of the primed CD8 cell repertoire induced by a minor transplantaiton antigen. J.Immunol . 165: 1278-1284.

Pelfrey, C. M., Rudick, R. A., Cotleur, A. C., Lee, J.-C., Tary-Lehmann, M., Lehmann, P. V. 2000. Quantification of self-recognition in multiple sclerosis by single-cell analysis of cytokine production. J. Immunol . 165: 1641-1651.

Targoni, O. S., Baus, J., Karulin, A. Y., Hofstetter, H. H., Boehm, B. B., Forsthuber, T., Lehmann, P. V. 2000. Frequencies of neuroantigen-specific T cells in the CNS versus the immune periphery during the course of EAE. J.Immunol. 166: 4757-4764.

Hesse, M. D., Karulin, A. Y., Boehm, O. B., Tary-Lehmann, M., Lehmann, P. V. T cell avidity is a function of the T cell's activation state. J. Immunol . 167:1353-1361.

Gottwein, J. M., Blanchard, T. G., Targoni, O. S., Eisenberg, J. G. C., Zagorski, B. M., Trezza, R. P., Redline, R. V., Nedrud, J. G., Tary-Lehmann, M., Lehmann, P. V.* and Czinn, S. J.* (contributed equally). 2000. Systemic vaccination with aluminum hydroxide induces protective immunity against Helicobacter pylori infection in mice. J. Infect. Dis . 184(3):308-314.

Karulin, A.Y., Hesse, M.D., Yip., H.C., and Lehmann, P.V. 2002, Indirect IL-4 pathway in Th1 immunity J. Immunol., 168:545-553.

Anthony, D.D., Post, A.B, Heeger, P.S., and Lehmann, P.V. 2002. Comprehensive determinant mapping of the Hepatitis-C-Virus specific CD8 cell repertoire reveals unpredicted immune hierarchy. Clin. Immunol . 103:264-276.

Hofstetter, H., Fabry Z. and Lehmann, P.V. 2002. Th1 and Th2-type autoimmune response to neuroantigen promotes tissue regeneration after cryoinjury. J. Neuroimmunol . . 134: 25 – 34

Schlingman, T.R., Rininsland, F. H., Bartholomae, W.C., Boehm, B.O, Lehmann, P.V. and Tary-Lehmann, M. 2002. Loading of Tumor with foreign antigen results in determinant spreading to tumor antigens. Nature Immunol. , Pending.

Guerkov, R. , Targoni, O.S., Kreher, C.R., Boehm, B.B., Tary-Lehmann, M., Lehmann, P.V*., Scwander, S.K*. 2003. Detection of low frequency antigen-specific IL-10-producing T cells via ELISPOT in PBMC: cognate vs non-specific production of the cytokine. (*contributed equally ). J. Immunol. Methods , 2003, 279:111-121

Eisenberg, J., Czinn, J.S., Garhard, C.A., Redline, R.W., Bartholomae, W.C., Gottwein, J., Nedrud, J.G., Emancipator, S.E., Boehm, B.B., Lehmann, P.V., and Blanchard, T.G. 2003. Protective efficacy of anti-Helicobacter pylori immunity following systemic immunization of neonatal mice. Infection and Immunity 71:1820-7

Lonsdorf A.S., Kuekrek H., Stern B.V., Boehm B.O., Lehmann P.V. and Tary-Lehmann M. Intratumor CpG-Oligodeoxynucleotide Injection Induces Protective Antitumor T Cell Immunity. J. Immunol. 2003, 171: 3941-3946.

Ott, P. A. Berner B.R., Herzog B.A., Guerkov R., Yonkers N.L., Boehm B.O., Durinovic-Bello I., Tary-Lehmann M., Lehmann P.V. and Anthony D.D. 2004. CD28 costimulation enhances the sensitivity of the ELISPOT assay for detection of antigen-specific memory effector CD4 + and CD8 + cell populations in human diseases . J. Immunol. Methods , 2004, 285: 223-235.

Patrick O. Ott, Marcus T Dittrich, Bernhard A. Herzog, Robert Guerkov, Peter A. Gottlieb, Amy L. Putnam, Ivana Durinovic-Bello, Bernhard O. Boehm, Magdalena Tary-Lehmann, Paul V. Lehmann: T cells recognize multiple GAD65 and Proinsulin epitopes in human type 1 diabetes, suggesting determinant spreading . J. Clin. Immunol ., 2004, 24: 458-470.

Darabi, K., Karulin, A.Y., Boehm, B.B., Hofstetter, H.H., Fabry, Z., LaManna, J. C., Chavez, J.C., and Lehmann, P.V. 2004. Third signal in T cell-mediated autoimmune disease, J. Immunol . (In press)

Herzog, B., Ott, P., M. Dittrich, M. Tary-Lehmann, P. V. Lehmann, B.O. Boehm, and Durinovich-Bello, I. Increased in vivo frequency of IA-2 peptide-reactive, IFN-gamma +/IL-4- T cells in type 1 diabetic subjects. J. Autoimmunity , 2004, In press

Anthony D. Yonkers N. L., Post, B. A., Asaad, R., Heinzel F. P., Lederman M. M., Lehmann, P.V., and Valdez H. Selective Impairments in Dendritic Cell-Associated Function Distinguish Hepatitis C Virus and HIV Infection 1 J. Immunol., 2004, 172: 4907-4916 .

RO1 NS39434-01A1 P.V. Lehmann (PI) 6/01/00 – 5/31/05
NIH
Natural history of the autoreactive T cell responses in EAE
Aim 1 is to define the population kinetics of the autoimmune T cell respnse in the course of EAE. Aim 2 is to test how measurements done on the blood reflect the fine specificity of the autoimmune repertoire in lymphoid tissues and the CNS. Aim 3 is to test for repertoire selection of the nueroantigen-specific T cell populations. Aims4 is to test whether the functionality of the autoimmune repertoire differs in anatomic compartments and changes in the course of EAE.
Role: PI, Grant to CWRU

RO1 AI-47839-01 P.V. Lehmann (PI) 6/01/00 - 5/31/05
NIH
Hepatitis C virus-specific T cell immunity
Aim 1 is to perform systematic ELISPOT determinant mapping with an overlapping HCV-core-peptide series to probe the magnitude and fine specificity of the T cell repsonse to HCV Core protein. Aim 2 is to define HCV-peptide-reactive T cells as CD4/CD8 and verify the frequency measurements. Aim 3 is to test for the coexpression of cytokine and granzyme B in individuals, freshly isolated HCV-peptide-reactive memory cells.
Role: Co-PI, Grant to CWRU

Juvenile Diabetes Foundation P.V. Lehmann (PI) 01/01/2000 – 12/31/2003
JDF
Tracing islet cell antigen reactive T cells after specific immune therapy
The specific aim of these studies to to uinderstand the population kinetics of the autoimmune T cell response and its compartmentalization in the NOD mouse and by doing so provide information that furthers the understanding of data obtained from testing the blood of patients with type-1 diabetes.
Role: PI Grant to CWRU

R01 AI-4775603 Tary-Lehmann (PI) 03/01/00 – 2/28/05
NIH
Single cell analysis of T cell immunity in HIV
We propose to use a new generation of image analysis-assisted ELISPOT assays to characterize at single-cell resolution the HIV antigen specific CD4 and CD8 cell activity in HIV-infected patients, their contact persons, and healthy donors that have not been exposed to HIV.
Role: Co-PI, Grant to CWRU

NIH, Immune Tolerance Network , ELISPOT monitoring of T cell Immunity/Tolerance. Principal investigator P.V. Lehmann. Funding period 01.05.2000 - 29.04.2005, C ntract for CTL ).

National Multiple Sclerosis Society. P.V. Lehmann (PI) RG 2897-A-2 04/01/97 - 03/31/2001
NMSS
The IFA induced T cell response to neuroantigens in EAE
The specific aims of this project are to characterize the MBP/IFA induced immune response and its consequence on the CNS. To characterize the PLP/IFA induced T cell response and its consequences on the CNS and to define in vivo whether the EAE protective mechanism induced by injection of myelin antigen in IFA is CD4 or CD8 cell mediated.
Role: PI

R29 DK-48799-01A1 Lehmann (PI) 07/01/95 - 06/30/2000
NIH
Autoimmune T cell responses in Murine Insulin Dependent Diabetes
Aim 1 of this project is to define T cell responses to beta cell antigen in murine IDDM. Aim 2. is to test whether initial autoimmunity to GAD triggers second wave autoimmunity to beta cell antigens.

R21DK-98-010 P.V. Lehmann (PI) 12/01/98 - 11/30/2000
NIH
Human/Humanized T cell response to islet cell antigens
The specific aims of this project are to test for CD8 cell responses to GAD65 and to test for reactivity of CD4 cells to cryptic GAD65 determinants.
Role: PI

R21 AI42635 P.V. Lehmann (PI) 03/30/98 - 09/29/99
NIH
Monitoring the CD8 response in HIV by ElisaSpot
Aim 1 of this project is to show feasibility of ELISA spot monitoring of CD8 cell function in the mouse. Aim 2 to show feasibility of ELISA spot monitoring of the anit-gag CD8 response in HIV infected humans.
Role: PI