Invariant NKT cells are required for antitumor responses induced by host-versus-graft responses.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Toshiki I SaitoMegan Sykes

Abstract

Based on clinical observations, we have previously shown in a murine model that recipient leukocyte infusion (RLI) induces a host-versus-graft reaction in mixed bone marrow chimeras and that rejection of donor cells leads to a specific antitumor response against recipient malignancies. This response is dependent on T cells and IFN-gamma. We investigated the role of NKT cells (NKTs) in this phenomenon. Depletion of recipient NK1.1(+) cells led to loss of an anti-tumor effect induced by RLI in mixed bone marrow chimeras. In recipients specifically lacking host invariant NKT cells (iNKTs), RLI did not induce an antitumor effect, indicating a critical role for recipient iNKTs. Conversely, specific activation of iNKTs enhanced the anti-tumor effect induced by RLI. Following RLI, recipient iNKTs, NK cells, dendritic cells (DCs), and CD8 T cells were activated. CD8 T cells were the major producers of IFN-gamma. Lack of recipient iNKTs resulted in failure of activation of NK cells and DCs by RLI. Our studies demonstrate a central role for iNKTs in promoting RLI-induced anti-tumor effects and suggest that this pathway involved promotion of the activation of recipient NK cells and DCs.

References

Jan 1, 1995·Immunogenetics·A A ScalzoG R Shellam
Apr 6, 1999·The Journal of Experimental Medicine·D ZengS Strober
Jul 7, 1999·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·M R PelotM Sykes
Feb 24, 2000·The Journal of Experimental Medicine·M J SmythD I Godfrey
Dec 18, 2001·Nature Immunology·Janice M KellyMark J Smyth
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Detlef StoberJörg Reimann
Jun 24, 2003·The Journal of Laboratory and Clinical Medicine·Pavan Reddy, James L M Ferrara
Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Constantin N BaxevanisMichael Papamichail
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ian F HermansVincenzo Cerundolo
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daigo HashimotoTakanori Teshima
Mar 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aki IshikawaTakehiko Fujisawa
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johnna D WesleyLaurent Brossay
Dec 8, 2006·Annual Review of Immunology·Albert BendelacLuc Teyton
Jan 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antony George JoyeeXi Yang

❮ Previous
Next ❯

Citations

May 26, 2012·Nature Reviews. Immunology·Hao Wei Li, Megan Sykes
Feb 9, 2012·Advances in Hematology·John L ReaganPeter J Quesenberry
Feb 13, 2014·Immunological Reviews·Ephraim J Fuchs
Jan 22, 2011·Blood·Stephen Mackinnon, Ronjon Chakraverty
Jun 19, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hao Wei LiMegan Sykes
Dec 1, 2014·Leukemia Supplements·J L Reagan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.