title: Type 1 diabetes development requires both CD4+ and CD8+ T cells and can be reversed by non-depleting antibodies targeting both T cell populations.
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 CD8alpha. It is known that CD8alpha is expressed not only on alphabeta 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 re-examined the need for both CD4(+) and CD8(+) T cell populations in diabetes development in NOD mice using an antibody to CD8beta. 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.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge, CB21 QP, United Kingdom.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Phillips
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Parish
authors.forename: Tim
authors.initials: T
authors.lastname: Raine
authors.forename: Chris
authors.initials: C
authors.lastname: Bland
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sawyer
authors.forename: Hugo
authors.initials: H
authors.lastname: De La Peña
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke