1 research outputs found
Investigation of Cytotoxic T Lymphocyte Function during Allorejection in the Anterior Chamber of the Eye
Cytotoxic T lymphocytes (CTL) are an essential part of our immune system by killing
infected and malignant cells. To fully understand this process, it is necessary to study CTL function
in the physiological setting of a living organism to account for their interplay with other immune
cells like CD4+ T helper cells and macrophages. The anterior chamber of the eye (ACE), originally
developed for diabetes research, is ideally suited for non-invasive and longitudinal in vivo imaging.
We take advantage of the ACE window to observe immune responses, particularly allorejection of
islets of Langerhans cells by CTLs. We follow the onset of the rejection after vascularization on
islets until the end of the rejection process for about a month by repetitive two-photon microscopy.
We find that CTLs show reduced migration on allogeneic islets in vivo compared to in vitro data,
indicating CTL activation. Interestingly, the temporal infiltration pattern of T cells during rejection
is precisely regulated, showing enrichment of CD4+ T helper cells on the islets before arrival of
CD8+ CTLs. The adaptation of the ACE to immune responses enables the examination of the
mechanism and regulation of CTL-mediated killing in vivo and to further investigate the killing in
gene-deficient mice that resemble severe human immune diseases