Abstract
The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. Although splenectomy remains a common procedure, recent studies reported poor prognosis and increased risk of haematological malignancies in asplenic patients. The high baseline trafficking of T lymphocytes to splenic tissue suggests splenectomy may lead to loss of blood-borne malignant immunosurveillance that is not compensated for by the remaining SLT. To date, no quantitative analysis of the impact of splenectomy on the human T cell trafficking dynamics and tissue localisation has been reported. We developed a quantitative computational model that describes organ distribution and trafficking of human lymphocytes to explore the likely impact of splenectomy on immune cell distributions. In silico splenectomy resulted in an average reduction of T cell numbers in SLT by 35% (95%CI 0.12–0.97) and a comparatively lower, 9% (95%CI 0.17–1.43), mean decrease of T cell concentration in SLT. These results suggest that the surveillance capacity of the remaining SLT insufficiently compensates for the absence of the spleen. This may, in part, explain haematological malignancy risk in asplenic patients and raises the question of whether splenectomy has a clinically meaningful impact on patient responses to immunotherapy.
Highlights
The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses
Since the spleen comprises a major part of the SLT, we sought to investigate how splenectomy affects the T cell distribution in other organs, the lymph nodes
Despite the high complexity of the trafficking model (101 parameters), the steady-state model reduction demonstrated that post- to pre-splenectomy cell concentration ratios across all organ compartments can be described by four variables
Summary
The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. APCs carrying cancer antigen migrate to secondary lymphoid tissue (SLT), where subsequent T cell activation occurs when a naïve immune T cell encounters an APC that presents antigen recognised by this T cell’s receptor (so-called cognate antigen). Such T cell activation events initiate adaptive immune responses, which drive the identification and selective clearance of abnormal human cells, further facilitating tumour infiltration, killing of cancer cells and antigen release, generating the tumour-immunity cycle. The continuous recirculation of T cells facilitates the detection and elimination of any invading pathogens, abnormal human cells or foreign particles[3]
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