IHV > Research : Cytokine Regulation of T Cells in HIV Disease
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Cytokine Regulation of T Cells in HIV Disease

Lab Head

Yutaka Tagaya 
Yutaka Tagaya
Assistant Professor, Principal Investigator

Exploring New Strategies

HIV infection is a very complex process. There is no doubt that CD4 T cells are the major target of the virus and an effective intervention requires the generation and participation of competent anti-HIV T cells. Dr. Tagaya’s research in the past has been focused on cytokine biology. Formerly, Dr. Tagaya’s group has discovered a unique mechanism of trans-cellular presentation of interleukin-15 and more recently a novel mechanism (pre-conditioning) that controls the responsiveness of naïve and resting T cells to cytokines. The working-hypothesis is that this process (pre-conditioning) controls the generation and longevity of memory T cells. Based on this discovery, the group is currently starting a new study to understand why T-cell memory cannot be efficiently established upon HIV infection. Thus the first research focus will be on the establishment of T cell memory upon HIV infection. Dr. Tagaya and co-workers recently discovered that a transcription factor called IRF-8 (Interferon Regulatory factor-8) plays a critical role in converging two distinct signals, that from the TCR and common-{alpha} cytokine receptor and thereby orchestrating the transition of naïve CD8 T cells into effector cells. Because of the suspected involvement of IRF-8 in the generation of anti-viral cytotoxic T cells, study of the expression state of this factor, as well as manipulation of its expression in HIV-positive T cells will be pursued as a parallel research focus because it may offer us a new perspective in enabling an effective anti-HIV immunity during the acute phase of HIV infection.

Select Recent Publications

Miyagawa F, Tagaya Y, Kim BS, Patel HJ, Ishida K, Ohteki T, Waldmann TA , and Katz SI. IL-15 serves as a co-stimulator in determining the activity of autoreactive CD8 Tcells in an experimental mouse model of graft vs. host like disease. J. Immunol. 2008 181: 1109-19

Terabe M, Tagaya Y, Roederer M, Waldmann TA, and Berzofsky JA. IL-15 expands unconventional CD8{alpha}{alpha}NK1.1+ T cells but not V{alpha}14J{alpha}18+NKT cells. J. Immunol. 2008 180: 7276-86

Sato N, Patel HJ, Waldmann TA, and Tagaya Y The IL-15/IL-15R{alpha} on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 T cells. Proc. Natl. Acad. Sci. USA 2007 104: 588-593

Kobayashi H, Dubois S, Sato N, Sabzevari H, Sakai Y, Waldmann TA, and Tagaya Y. The role of trans-cellular IL-15-presentation in the activation of NK-mediated killing, which leads to enhanced tumor immunesurveillance. Blood, 2005 105: 721 – 727

Dubois S, Mariner J, Waldmann TA, and Tagaya Y. IL-15R{alpha} recycles and presents IL-15 in trans to neighboring cells. Immunity 2002 17: 537-547.

Marks-Konczalik J, Dubois S, Sabzevari H, Yamada N, Feigenbaum L, Waldmann TA, and Tagaya Y. IL-2 induced activation-induced cell death is inhibited in IL-15 Transgenic mice. Proc. Natl. Acad. Sci. 2000 97:11445-11450