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

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.