Makio Iwashima, Ph.D.
Associate Professor

Ph.D., Stanford University

Molecular & Cellular Immunologist

Cell biology of T cell subsets

T lymphocytes play critical roles in immune responses against infections and tumors. The majority of T lymphocytes are called effector cells. They function in the first line of host defense by producing cytokines, inducing antibody formation, and directly killing infected or transformed cells. Many effector T cells die after completing their responses against antigens, but a group of effector cells remain in the periphery and survive for a long period of time as "memory" T cells. These memory T cells play a critical role in the maintenance of immunological memory and are key for effective vaccination. The loss of memory T cells contributes to the impairment of the immune responses in aged populations.

Another small group of T cells, called regulatory T cells, plays a significant role in suppressing unwanted immune responses against self-antigens. Decreased numbers of regulatory T cells, or impairment of their function, leads to autoimmune disorders such as Type I diabetes or inflammatory bowel disease. Conversely, increased numbers of regulatory T cells may contribute to chronic infectious diseases or growth of tumors. 
 
Our main research interest is to elucidate the molecular and cellular characteristics of memory and regulatory T cells. The main questions that we address are: 
(1) How do memory T cells survive in vivo for a long time? 
(2) How is the balance between regulatory and effector T cells controlled?
(3) How do regulatory T cells control immune responses?

We have developed procedures to isolate and expand these minor fractions of T cells and we are examining them in detail by proteomic, genomic, and imaging analysis. Successful completion of these studies will potentially lead to treatment for autoimmune disorders, enhancement of immune response against tumors, and development of vaccine effective for immunocompromised individuals. 

Selected Publications

Braun RK, Martin A, Shah S, Iwashima M, Medina M, Byrne K, Sethupathi P, Wigfield CH, Brand DD, Love R. Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type V. J Heart Lung Transplant. 2010 Aug; 29(8):873-80. Epub 2010 May 14

Singh N, Yamamoto M, Takami M, Seki Y, Takezaki M, Mellor AL, Iwashima M. CD4(+)CD25(+) regulatory T cells resist a novel form of CD28- and Fas-dependent p53-induced T cell apoptosis. (2010) J Immunol. 184(1):94-104. Epub 2009 Nov 30.PMID: 19949106 [PubMed - in process]

Chang JW, Koike T, Iwashima M. hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation. (2009) Int Immunol. 21(12):1351-61. Epub 2009 Oct 30.

Singh N., Chandler, P.R., Seki, Y., Baban, B., Takezaki, M., Kahler, D.,Munn D.H., Larsen, C.P., Mellor, A.L., and Iwashima M.Role of CD28 in lethal lymphoproliferative disease in scurfy mice.Blood, 110(4):1199-206.

Pacholczyk, R., Kern, J., Singh, N., Iwashima, M., Kraj, P., and Ignatowicz, L. Non-self antigens are the cognate specificities of Foxp3+ TR cells. (2007)  Immunity, 27(3):493-504. 

Singh N., Seki, Y., Takami, M., Baban, B., Chandler, P.R., Khosravi, D., Zheng, X., Takezaki, M., Lee, J.R., Mellor, A.L., Bollag, W.B., and Iwashima, M.  Enrichment of regulatory CD4+CD25+ T cells by inhibition of Phospholipase D signaling. (2006)  Nature Methods  3(8):629-36.

Fukushima, A., Hatanaka, Y., Takamatsu, M., Chang, J.W, Singh, N., and Iwashima, M. Lck couples Shc to TCR signaling. (2006)  Cell. Signal. 18(8):1182-9.

Iwai, K, Lee, B.R., Hashiguchi, M., Fukushima, A., and Iwashima, M.  IkB-α specific transcription regulation by the C-terminal end of c-Rel. (2005)  FEBS letter,  579:141-4.

Ohtsuka M., Asase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T., Sakurai D., Yokosuka T., Asase N., Iwashima, M., Kitamura T., Moriya H., and Saito T., NFAM1, a new ITAM surface molecule that regulates development and signaling of B lymphocytes. (2004)  Proc. Natl. Acad. Sci. USA,  101:8126-31.

Mellor, A.L., Baban, B., Chandler, P., Marshall, B., Jhaver, K., Hansen, A., Koni, P.A., Iwashima, M., and Munn, D.H.,  Induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. (2003) J. Immunol. 171:1652-5.

Iwashima, M. Kinetic perspectives of T cell activation. (2003) Immunol. Rev. 192. 196-210.

Koike, T., Yamagishi, H., Hatanaka Y., Fukushima A., Chang, J.W., Xia, Y., Fields, M., Chandler, P., and Iwashima, M. A novel ERK dependent signaling process that regulates IL-2 expression in a late phase of T cell activation. (2003)  J. Biol. Chem.   278:15685-92. 

Iwashima, M., Takamatsu, M, Yamagishi,H., Huang, Y., McGinty, C., Hatanaka, Y., Yamasaki, S., and Koike, T. Genetic evidence for Shc requirement in TCR induced c-Rel activation and IL-2 expression. (2002)  Proc. Natl. Acad. Sci. USA   99:4544-4549.