Department of Pathology, Microbiology, and Immunology



Danyvid Olivares-Villagomez, Ph.D.



Research Associate Professor

Dept of Pathology, Microbiology and Immunology



Contact Information



Office Location:
AA-5206 MCN

Phone: 615-343-2708
E-mail:  danyvid.olivares-villagomez@Vanderbilt.Edu


Campus Mail address:

Pathology, Microbiology and Immunology-5th Fl

A-5301 MCN (2363)


US Mailing address:

Vanderbilt University School of Medicine

Dept Pathology, Microbiology and Immunology-5th Fl
MCN A-5301
1161 21st Ave. S.

Nashville, TN 37232-2363



Research Keywords



Mucosal immunology, intraepithelial lymphocytes, thymus leukemia (TL) antigen.



Research Description



Our bodies are constantly exposed to infectious agents wanting to invade and cause harm. One of the areas with high exposure to foreign antigens is the mucosa of the digestive tract. The mucosal immune system protects the intestines from pathogenic invaders and at the same time discriminates those organisms that are important for our overall homeostasis. My research focuses in the role of a molecule conspicuously expressed in the intestinal epithelial cells (IEC), known as thymus leukemia (TL) antigen, and its interaction with CD8alpha homodimers expressed by intestinal intraepithelial lymphocytes (IEL).

IEL are a group of lymphocytes that in the mouse are comprised primarily of TCRalpha-beta and TCRgamma-delta cells. The great majority of these cells express CD8alpha-alpha. It is thought that TL on IEC interacts and modulates the response of CD8alpha-alpha+ cells. To understand the role of the CD8alpha-alpha-TL interaction, we developed a mouse line that lacks expression of TL. We showed that IEL from TL-deficient mice proliferate more in vivo and in vitro, are more cytotoxic and produce larger amounts of IFN-gamma. Moreover, when TL-deficient mice were crossed with TCRalpha-deficient animals (a susceptible strain of mice for the development of IBD), we observed that TL-deficiency increases the severity and the onset of IBD. These results indicate that TL functions as a check point for the prevention of IBD.

My current research is trying to understand the molecular mechanisms governing the interaction of TL-CD8alpha-alpha, and how lymphocytes respond in the absence of these two molecules.






Huang, Y., Park, Y., Wang-Zhu, Y., Larange, A., Arens, R., Bernardol, I., Olivares-Villag??mez, D., Herndler-Brandstetter, D., Abraham, N., Grubeck-Loebenstein, B., Schoenberger, S.P., Van Kaer, L., Kronenberg, M., Teitell, A., and Cheroutre, H. Mucosal CD8 memory T cells are selected in the periphery by an MHC class I molecule. Nature Immunology, In press

Olivares-Villag??mez, D, Algood, HM, Singh, K, Parekh, VV, Ryan, KE, Piazuelo, MB, Wilson, KT, Van Kaer, L. Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen. J Immunol, 187(8), 4051-60, 2011

Goettel, JA, Scott Algood, HM, Olivares-Villag??mez, D, Washington, MK, Chaturvedi, R, Wilson, KT, Van Kaer, L, Polk, DB. KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-I? production. Gastroenterology, 140(1), 265-74, 2011

Olivares-Villag??mez, D, Van Kaer, L. TL and CD8I?I?: Enigmatic partners in mucosal immunity. Immunol Lett, 134(1), 1-6, 2010

Olivares-Villag??mez, D, Mendez-Fernandez, YV, Parekh, VV, Lalani, S, Vincent, TL, Cheroutre, H, Van Kaer, L. Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease. Proc Natl Acad Sci U S A, 105(46), 17931-6, 2008

Yan, J, Parekh, VV, Mendez-Fernandez, Y, Olivares-Villag??mez, D, Dragovic, S, Hill, T, Roopenian, DC, Joyce, S, Van Kaer, L. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J Exp Med, 203(3), 647-59, 2006

Curotto de Lafaille, MA, Shen, S, Olivares-Villag??mez, D, Camps-Ram?-rez, M, Lafaille, JJ. Do regulatory T cells play a role in the control of homeostatic proliferation. Int Rev Immunol, 24(3-4), 269-84, 2005

Shen, S, Ding, Y, Tadokoro, CE, Olivares-Villag??mez, D, Camps-Ram?-rez, M, Curotto de Lafaille, MA, Lafaille, JJ. Control of homeostatic proliferation by regulatory T cells. J Clin Invest, 115(12), 3517-26, 2005

Parekh, VV, Wilson, MT, Olivares-Villag??mez, D, Singh, AK, Wu, L, Wang, CR, Joyce, S, Van Kaer, L. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J Clin Invest, 115(9), 2572-83, 2005

Parekh, VV, Singh, AK, Wilson, MT, Olivares-Villag??mez, D, Bezbradica, JS, Inazawa, H, Ehara, H, Sakai, T, Serizawa, I, Wu, L, Wang, CR, Joyce, S, Van Kaer, L. Quantitative and qualitative differences in the in vivo response of NKT cells to distinct alpha- and beta-anomeric glycolipids. J Immunol, 173(6), 3693-706, 2004

Lane, JE, Ribeiro-Rodrigues, R, Olivares-Villag??mez, D, Vnencak-Jones, CL, McCurley, TL, Carter, CE. Detection of Trypanosoma cruzi DNA within murine cardiac tissue sections by in situ polymerase chain reaction. Mem Inst Oswaldo Cruz, 98(3), 373-6, 2003

Wilson, MT, Johansson, C, Olivares-Villag??mez, D, Singh, AK, Stanic, AK, Wang, CR, Joyce, S, Wick, MJ, Van Kaer, L. The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc Natl Acad Sci U S A, 100(19), 10913-8, 2003

Zhang, J, Dong, M, Li, L, Fan, Y, Pathre, P, Dong, J, Lou, D, Wells, JM, Olivares-Villag??mez, D, Van Kaer, L, Wang, X, Xu, M. Endonuclease G is required for early embryogenesis and normal apoptosis in mice. Proc Natl Acad Sci U S A, 100(26), 15782-7, 2003

Furtado, GC, Olivares-Villag??mez, D, Curotto de Lafaille, MA, Wensky, AK, Latkowski, JA, Lafaille, JJ. Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol Rev, 182, 122-34, 2001

Singh, AK, Wilson, MT, Hong, S, Olivares-Villag??mez, D, Du, C, Stanic, AK, Joyce, S, Sriram, S, Koezuka, Y, Van Kaer, L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J Exp Med, 194(12), 1801-11, 2001

Curotto de Lafaille, MA, Muriglan, S, Sunshine, MJ, Lei, Y, Kutchukhidze, N, Furtado, GC, Wensky, AK, Olivares-Villag??mez, D, Lafaille, JJ. Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J Exp Med, 194(9), 1349-59, 2001

Olivares-Villag??mez, D, Wensky, AK, Wang, Y, Lafaille, JJ. Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis. J Immunol, 164(10), 5499-507, 2000

Olivares-Villag??mez, D, McCurley, TL, Vnencak-Jones, CL, Correa-Oliveira, R, Colley, DG, Carter, CE. Polymerase chain reaction amplification of three different Trypanosoma cruzi DNA sequences from human chagasic cardiac tissue. Am J Trop Med Hyg, 59(4), 563-70, 1998

Olivares-Villag??mez, D, Wang, Y, Lafaille, JJ. Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis. J Exp Med, 188(10), 1883-94, 1998

Lane, JE, Olivares-Villagomez, D, Vnencak-Jones, CL, McCurley, TL, Carter, CE. Detection of Trypanosoma cruzi with the polymerase chain reaction and in situ hybridization in infected murine cardiac tissue. Am J Trop Med Hyg, 56(6), 588-95, 1997