Abstract
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.
Highlights
Cytotoxic T lymphocytes (CTLs) play an important role in the adaptive immune system
We demonstrated alloreactive T cell migration and their attack on islets of Langerhans in vitro by confocal microscopy
To account for the complexity of the immune system response to allografts, we further investigated the activity of CTLs in vivo on the transplanted islet in the anterior chamber of the eye (ACE) by two-photon microscopy
Summary
Cytotoxic T lymphocytes (CTLs) play an important role in the adaptive immune system. They fight against tumor and virus-infected cells through delivery of cytotoxic components to target cells, thereby inducing apoptotic death. TCR engagement leads to T cell activation and this engagement triggers the accumulation of signaling molecules at the contact site between CTL and target cell, the immunological synapse (IS). CTLs fulfill their killing task by releasing cytotoxic substances like granzyme B (GzmB) and perforin from CG onto the target cell. Due to their cytotoxicity, CTLs play an important role in allograft rejection, mainly to destroy the foreign tissue to maintain the physiological integrity of the organism
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