Research Faculty

630 West 168th Street
VC 15-204
New York, NY 10032

Phone: 212-305-6941
Fax: 212-305-3429
Education and Training
B.S. University of Bucharest, 1959
M.S. University of Bucharest, 1961
Ph.D. University of Bucharest, 1969

Institute for Cancer Genetics

Intl Collaborations
Interuniversitary Consortium for Organ Transplantation
University of Genova

Nicole Suciu-Foca, Ph.D.
Professor of Pathology and Cell Biology
Research Summary

Allograft rejection is a complex phenomenon that involves both the cellular and humoral arm of the immune response. This process is triggered by disparate histocompatibility antigens expressed by graft tissue and recognized by recipient T and B lymphocytes. There are two pathways by which T cells may recognize MHC alloantigens. The direct pathway involves T cell recognition of intact MHC molecules expressed by donor APC. The second, or indirect, pathway describes T cell recognition of peptides derived from the processing and presentation of allogeneic MHC molecules on self-antigen-presenting cells.

Studies performed in our laboratory have demonstrated the crucial role of indirect alloreactivity in both acute and chronic rejection of human organ allografts. We showed that rejection is initiated by a clonal population of T cells, which recognize a unique immunodominant peptide derived from the hypervariable region of a donor HLA-DR molecule. T cell reactivity to immunodominant peptides of donor MHC antigens is an early indicator of transplant rejection. During recurring episodes of acute rejection as well as at the onset of chronic rejection intra and intermolecular spreading of T cell epitopes occurs. T cells recognizing cryptic epitopes of the same molecule or determinants of another mismatched HLA-DR antigen become activated, contributing to the amplification and perpetuation of the immune response.

Alloreactivity, however, can be inhibited by a subset of T lymphocytes with suppressor function. We demonstrated that T suppressor cells express the CD3+CD8+CD28-phenotype, use a restricted repertoire of TCR Vb genes and recognize peptides presented by MHC class I molecules. These CD8+CD28- T cells suppress the activation of CD4+ T helper cells by inducing the down-regulation of costimulatory molecules CD40, CD80 and CD86 and upregulation of the inhibitory receptors ILT3 and ILT4 in antigen presenting cells (APC).

Using molecular and cellular immunology techniques, we further established that the inhibitory receptors ILT3 and ILT4 are crucial to the tolerogenic phenotype acquired by professional and non-professional APC, such as dendritic and endothelial cells, respectively. The bi-directional interaction between APC and T suppressor cells triggers a cascade of events which results in graft adaptation and T cell unresponsiveness to alloantigens presented via the direct and indirect pathway.

We have engineered a recombinant ILT3-Fc protein and demonstrated that this agent alone, without any complementary iatrogenic immunosuppression inhibits xenospecific GVHD and induces allogeneic tolerance to human pancreatic islets in a humanized NOD/SCID mouse model. ILT3-Fc induces the upregulation of BCL6, DUSP10, TGFβR2, CXCR4 and SOCS1 both in vivo and in vitro. The up-regulation of these genes with immunoregulatory function is caused by the ILT3-Fc induced down-regulation of proinflammatory miRNA which target their 3’UTR region. Our studies support the high potential of ILT3-Fc as an immunosuppressive agent in transplantation and autoimmune diseases.
Selected Publications

1. Chen L, Xu Z, Chang C, Ho S, Liu Z, Vlad G, Cortesini R, Clynes RA, Luo Y, Suciu-Foca N. Allospecific CD8 T suppressor cells induced by multiple MLC stimulation or priming in the presence of ILT3.Fc have similar gene expression profiles. Hum Immunol. 2013 Nov 9. doi:pii: S0198-8859(13)00563-6. 10.1016/j.humimm.2013.10.004. [Epub ahead of print]

2. Chang CC, Zhang QY, Liu Z, Clynes RA, Suciu-Foca N, Vlad G. Downregulation of Inflammatory MicroRNAs by Ig-like Transcript 3 Is Essential for the Differentiation of Human CD8+ T Suppressor Cells. J Immunol. 188(7):3042-52, 2012.

3. Vlad G, King J, Chang CC, Liu Z, Friedman RA, Torkamani AA, Suciu-Foca N. Gene profile analysis of CD8(+) ILT3-Fc induced T suppressor cells. Hum Immunol. 72(2):107-14, 2011.

4. Chang CC, Vlad G, D’Agati VD, Liu Z, Zhang QY, Witkowski P, Torkamani AA, Stokes MB, Ho EK, Cortesini R, Suciu-Foca, N. BCL6 is required for differentiation of ILT3-Fc induced CD8+ T suppressor cells. J Immunol. 185(10):5714-22, 2010.

5. Chang CC, Liu Z, Vlad G, Qin H, Qiao X, Mancini DM, Marboe CC, Cortesini R, Suciu-Foca N. Ig-like transcript 3 regulates expression of proinflammatory cytokines and migration of activated T cells. J Immunol. 1;182(9):5208-16, 2009.

6. Vlad G, Stokes MB, Liu Z, Chang CC, Sondermeijer H, Vasilescu ER, Colovai AI, Berloco P, D'Agati VD, Ratner L, Cortesini R, Suciu-Foca N. Suppression of xenogeneic graft-versus-host disease by treatment with immunoglobulin-like transcript 3-Fc. Hum Immunol. 70(9):663-9, 2009.

7. Vlad G, D'Agati VD, Zhang QY, Liu Z, Ho EK, Mohanakumar T, Hardy MA, Cortesini R, Suciu-Foca N. ILT3-Fc suppresses T cell responses to allogeneic human islet transplants in Hu-NOD/SCID mice. Diabetes 57(7):1878-86, 2008.

8. Suciu-Foca N, Feirt N, Zhang QY, Vlad G, Liu Z, Lin H, Chang CC, Ho EK, Colovai AI, Kaufman H, D'Agati VD, Thaker HM, Remotti H, Galluzzo S, Cinti P, Rabitti, C, Allendorf A, Chabot J, Caricato M, Coppola R, Berloco P, Cortesini R. Soluble Ig-Like Transcript 3 Inhibits Tumor Allograft Rejection in Hu-SCID Mice and T Cell Responses in Cancer Patients. J Immunol. 178(11):7432-41, 2007.

9. Kim-Schulze, Scotto L, Vlad G, Piazza F, Lin H, Liu Z, Cortesini R, Suciu-Foca N. Recombinant Ig-Like Transcript 3-Fc Modulates T Cell Responses via Induction of Th Anergy and Differentiation of CD8+ T Suppressor Cells. J Immunol. 176(5):2790-8, 2006.

10. Kim-Schulze S, Seki T, Vlad G, Scotto L, Fan J, Colombo PC, Liu J, Cortesini R, Suciu-Foca N. Regulation of ILT3 Gene Expression by Processing of Precursor Transcripts in Human Endothelial Cells. Am J Transpl, 6(1):76- 82, 2005.

11. Vlad G, Cortesini R, Suciu-Foca N. License to Heal: Bidirectional Interaction of Antigen-Specific Regulatory T Cells and Tolerogenic APC. J Immunol. 174(10): 5907-14, 2005.

12. Manavalan JS, Kim-Schulze S, Scotto L, Naiyer AJ, Vlad G, Colombo PC, Marboe C, Mancini D, Cortesini R, Suciu-Foca N. Alloantigen specific CD8+CD28- FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells inhibiting alloreactivity. Int Immunol. 16(8):1055-1068, 2004.

13. Chang CC, Ciubotariu R, Cortesini R, Colonna M, Lederman S, Dalla-Favera R, Suciu-Foca N. Tolerization of dendritic cells by T(s) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 3(3):237-243, 2002.

14. Ciubotariu R, Colovai AI, Pennesi G, Liu Z, Smith D, Berlocco P, Cortesini R, Suciu-Foca N. Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28- regulatory T cells. J. Immunol. 161:5193-5202, 1998.

15. Ciubotariu R, Liu Z, Colovai AI, Ho E, Itescu S, Ravalli S, Hardy MA, Cortesini R, Rose EA, Suciu-Foca N. Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts. J. Clin. Invest. 101:398-405, 1998.

16. Liu Z, Colovai AI, Tugulea S, Reed EF, Fisher PE, Mancini D, Rose EA, Cortesini, R, Michler RE and Suciu-Foca N. Indirect recognition of donor HLA-DR peptides in organ allograft rejection. J. Clin. Invest. 98:1150-1157, 1996.

17. Harris PE, Maffei A, Colovai AI, Kinne J, Tugulea S, Suciu-Foca N. Predominant HLA-class II bound self peptides of a hematopoietic progenitor cell line. Blood 87:5104-5112, 1996.

18. Liu Z, Sun YK, Xi YP, Maffei A, Reed E, Harris P, Suciu-Foca N. Contribution of direct and indirect recognition pathway to T cell alloreactivity. J. Exp. Med. 177:1643-1650, 1993.

19. Harris PE, Lupu F, Hong B, Reed EF, Suciu-Foca N. Differentiation stage specific "self" peptides bound by MHC-class I molecules. J. Exp. Med. 177:783-790, 1993.

20. Liu Z, Sun YK, Xi YP, Harris P, Suciu-Foca N. T cell recognition of self-human histocompatibility leucocyte antigens (HLA)-DR peptides in context of syngeneic HLA-DR molecules. J. Exp. Med. 175:1663-1668, 1992.

21. Harris PE, Strba-Cechova K, Rubinstein P, Mann D, King DW, Suciu-Foca N. Amplification of T cell blastogenic responses in healthy individuals and patients with acquired immunodeficiency syndrome. J. Clin. Invest. 85:746-756, 1990.

22. Reed E, Hardy M, Benvenisty A, Lattes C, Brensilver J, McCabe R, Reemstma K, King DW, Suciu-Foca N. Effect of anti-idiotypic antibodies to HLA on graft survival in renal-allograft recipients. New Engl. J. Med. 316:1450-1455, 1987.

23. Sangster RN, Minowada, J, Suciu-Foca N, Minden M, Mak TW. Rearrangement and expression of the α, β, and γ chain T cell receptor genes in human thymic leukemia cells and functional T cells. J. Exp. Med. 163:1491-1508, 1986.

24. Suciu-Foca N, Reed E, Rubinstein P, MacKenzie W, Ng A, King DW. A late differentiation antigen (LDA1) associated with the helper inducer function of human T lymphocytes. Nature 318:465-467, 1985.

25. Kronenberg M, Goverman J, Haars R, Malissen M, Kraig E, Phillips L, Delovitch T, Suciu-Foca N, Hood L. Rearrangement and transcription of the beta-chain genes of the T cell antigen receptor in different types of murine lymphocytes. Nature 313:647-653, 1985.

26. Toyonaga B, Yanagi Y, Suciu-Foca N, Mindem M, Mak TW. Rearrangements of the T cell receptor gene YT35 in human DNA from thymic leukemic T cell lines and functional helper, killer and suppressor T cell clones. Nature. 311:385-387, 1984.

27. Yoshikai Y, Yanagi Y, Suciu-Foca N, Mak TW. Presence of T cell receptor mRNA in functionally distinct T cells and elevation during intrathymic differentiation. Nature 310:506-508.1984.

28. Suciu-Foca N, Rubinstein P, Popovic M, Gallo RC, King DW. Reactivity of HTLV transformed human T cell lines to MHC Class-II antigens. Nature 321:275-277, 1984.

Honors and Awards

Cum Laude

PhD, Magna Cum Laude

1969 - 1971
Eleanor Roosevelt Fellowship for Cancer Research at Memorial Sloan-Kettering Cancer Institute.

1980, 1984, 1990
International Histocompatibility Workshop Award for best Scientific performance.

National Institutes of Allergy and Infectious Diseases Study Section

Vice President, Organizing Committee, XVIII International Congress of the Transplantation Society

September, 2002
Awarded the National Order 'For Merit' with the degree of Commander (Star of Romania) from the President of Romania for remarkable scientific contribution in the field of Immunology and Genetics.

October, 2002
American Society for Histocompatibility and Immunogenetics (ASHI) Distinguished Scientist Award.

October, 2006
Awarded the American Society for Histocompatibility & Immunogenetics (ASHI) Rose Payne Award.
Committees , Council, and Professional Society Memberships

American Society of Transplantation (AST)

American Society for Histocompatibility and Immunogenetics (ASHI)

American Association for the Advancement of Science (AAAS)

The American Association of Immunologists (AAI)

The Transplantation Society

International Society for Heart and Lung Transplantation (ISHLT)

New York Academy of Sciences

HLA et Medicine

International Transplantation Society

Contact the Pathology Webmaster at