Type 1 Diabetes Development Requires Both CD4+ and CD8+ T cells and Can Be Reversed by Non-Depleting Antibodies Targeting Both T Cell Populations

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Abstract
The Review of Diabetic Studies,2009,6,2,97-103.
Published:August 2009
Type:Original Article
Authors:
Author(s) affiliations:

Jenny M. Phillips, Nicole M. Parish, Tim Raine, Chris Bland, Yvonne Sawyer, Hugo De La Peña and Anne Cooke

Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge, CB21 QP, United Kingdom.

Abstract:

Type 1 diabetes development in NOD mice appears to require both CD4+ and CD8+ T cells. However, there are some situations where it has been suggested that either CD4+ or CD8+ T cells are able to mediate diabetes in the absence of the other population. In the case of transgenic mice, this may reflect the numbers of antigen-specific T cells able to access the pancreas and recruit other cell types such as macrophages leading to a release of high concentrations of damaging cytokines. Previous studies examining the requirement for CD8+ T cells have used antibodies specific for CD8α. It is known that CD8α is expressed not only on αβ T cells, but also on other cell types, including a DC population that may be critical for presenting islet antigen in the pancreatic draining lymph nodes. Therefore, we have reexamined the need for both CD4+ and CD8+ T cell populations in diabetes development in NOD mice using an antibody to CD8β. Our studies indicate that by using highly purified populations of T cells and antibodies specific for CD8+ T cells, there is indeed a need for both cell types. In accordance with some other reports, we found that CD4+ T cells appeared to be able to access the pancreas more readily than CD8+ T cells. Despite the ability of CD4+ T cells to recruit CD11b class II positive cells, diabetes did not develop in the absence of CD8+ T cells. These studies support the observation that CD8+ T cells may be final effector cells. As both T cell populations are clearly implicated in diabetes development, we have used a combination of non-depleting antibodies to target both CD4-positive and CD8-positive cells and found that this antibody combination was able to reverse diabetes onset in NOD mice as effectively as anti-CD3 antibodies.