Regulatory T cells (Tregs) limit the onset of effective anti-tumor immune responses

Data was obtained on the regulatory T cells (Tregs) and their role in effective anti-tumor immune responses in FoxP3-DTR DEREG mice.

Although multiple mechanisms of Treg action have been proposed, the actual mechanism involved in the suppression of anti tumor T cell responses are still unclear.
Treg inactivation by anti-CD25 antibodies or by depletion in FoxP3-DTR DEREG mice resulted in effective rejection of the tumors upon adoptive transfer of antigen-specific CD8+ T cells. Treg inactivation or depletion induces a marked arrest in the migration of anti-tumor CD8+ T cells selectively in tumor-draining lymph nodes. Reduced T cell motility in lymph nodes was associated with an amplification of the effector cells, increased IFN? production, and tumor rejection.
We also show that Tregs make multiple brief contacts with the CD8+ T cells in the lymph nodes of tumor bearing mice. The frequency of these interactions, but not their duration, was inhibited by the treatment with anti-CD25 antibodies. We conclude that direct contacts between CD8+ T cells and Tregs in tumor-draining lymph nodes may contribute to the inhibition of anti-tumor immune responses. However, we were unable to establish the functional relevance of the direct Treg-CD8+ T cell contacts that we imaged.
Besides, Treg inactivation also induces an increase in the number of dendritic cells (DCs) in these tumor-draining lymph nodes. Therefore Tregs could influence CD8+ T cell arrest by modulating the number of antigen presenting cells in the tumor-draining lymph nodes.

DCs have developed numerous specializations to adapt their internalization pathway to efficient antigen processing. Recruitment of ER components to phagosomes has been postulated as one of the high specializations required to allow exogenous antigens to reach MHC class I pathway. However, no direct evidence of a fusion between those compartments has been reported. We will use a lentiviral-based approach to knock down protein expression of molecules potentially involved in ER-phagosome and we will test how this affect cross presentation in BMDCs.
Also, we are planning to investigate the mechanisms by which Tregs limit DC accumulation in tumor-draining lymph nodes. Preliminary results suggest that Treg may reduce DC survival in tumor draining lymph nodes. Therefore, we will use two photon microscopy to analyse DC survival in vivo and unravel the molecular mechanisms involved.

• organism type
• Mus musculus

• cell type
• dendritic cell,
• regulatory t cell

• molecule type
• CD8,
• interferon,
• CD25 receptor

• organ type
• human lymph node

created over 15 years ago (7 December 2009)    last modified over 12 years ago (8 October 2012)   [ RDF ]   [ RelFinder ]