News & Research

    Torrey Pines Institute for Molecular Studies, San Diego, California

Phenotypic and functional characterization of memory CD4 T cells in Type 1 Diabetes

General Research Subject: Type 1 Diabetes

Focus: Adipocytes, Immunology, Other, Transplantation

Type of Grant: Minority Undergraduate Internship

Project Start Date: January 1, 2013

Project End Date: December 31, 2013

Diabetes Type: Type 1 diabetes

Research Description

After contact with a particular antigen, memory T cells can divide very fast and this increases their potential to induce tissue damage leading to type 1 Diabetes (T1D). It is generally accepted that memory cells play an important role in T1D. There are different subsets of cells within the memory cell population, some are pathogenic and other not. The goal of this study is to identify those cells that are pathogenic, and in the long term, target those cells as part of a therapeutic strategy to treat T1D.

Mr. Escobedo will analyze different memory T cell populations that might participate in the development of T1D through a detailed analysis of functional markers that these cells express on their cell surface. He will be trained in multicolor flow cytometric analysis, a state of the art technology to analyze the internal and cell surface markers of these populations of memory cells. He will use NOD mice, the mouse model for spontaneous T1D, to investigate these cells during the natural course of the disease and after islet transplantation where memory T cells can be reactivated to destroy the transplant. Using this model system, he will identify T cells that are either associated with T1D onset, or T1D protection.

Research Profile

Mentor: Idania Marrero
Undergraduate: Christian Escobedo

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?

We have been studying the autoimmune disease T1D to identify the aggressive immune cells called memory CD4 T cells and their involvement in T1D. These autoreactive memory CD4 T cells are important because they actively destroy the patient islet β cells that produce insulin. Moreover, they can be reactivated following islet transplantation. Our aims are to investigate the characteristics and frequency of different memory CD4 T cell clones within the pool of memory CD4 T cells that are relevant to T1D. There is significant hope that our results can be translated towards specific therapeutic strategies to inhibit, neutralize and destroy these aggressive memory CD4 T cells.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

We are investigating the immune cells that destroy the insulin-producing islet β cells. These aggressive immune cells live for a long time and are called memory CD4 T cells. We are using a powerful state of the art technology to sequence the immune receptor on the surface of memory CD4 T cells. This information, in combination with functional studies, will allow us to identify the memory CD4 T cell repertoire that emerges during progression toward diabetes and after diabetes has been diagnosed. We hope to be able to identify and target dangerous cell populations in T1D patients to protect the islet cells from further damage.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?

I have been involved in diabetes research throughout my postdoctoral career. Research in T1D has been particularly important to me because I have the opportunity to apply the knowledge that I have gained regarding the basic immunological pathways to clinical medicine. It is my hope that knowledge gained in the study proposed will have a direct impact on the treatment and/or prevention of T1D. Specifically, we hope to gain new knowledge that will indicate how to eliminate the memory CD4 T cells that destroy beta cells in the patient pancreas and destroy islet grafts. This award will allow me to continue my career in diabetes research and explore new pathways involved in T1D that might provide new therapeutic strategies and successful treatments.

In what direction do you see the future of diabetes research going?

The future of diabetes research will be dependent on our capacity to translate the discovery of basic research to clinical practice. It is critical that we share our knowledge and promote strong collaborations in the scientific community. From our point of view, it will be important to combine molecular approaches, and sophisticated technology with the more basic approach of understanding the identity of the effectors cells that are involved in T1D.