Lymphocyte Migration Patterns in Organ Allograft Recipients

Abstract

A central tenet of immunology is the observation, made 30 years ago, that lymphocytes recirculate continuously between peripheral blood and lymphoid tissues. In recent years, the subject of lymphocyte migration, both under physiological conditions and in states of alloresponsiveness, has become more enigmatic. It lies outside most current topics of immunological investigations, labelling and tracing techniques are problematic, and many experimental findings are phenomenological and difficult to interpret. Indeed, our overall knowledge of the functional differences between the various host lymphoid compartments and their constituent cell populations remains rudimentary. However, as understanding increases regarding the host immunological events responding to an antigenic stimulus such as a graft, with growing definition of the distinctive and interconnecting roles of lymphocyte subpopulations and their products acting on each other to produce graft destruction, the conceptual importance of lymphocyte migration again is becoming obvious. This role includes many facets of immunity such as the effects of antigen specificity, immunologic memory, differential behavior of recirculating or sessile populations, and local and systemic contact between antigen and effector cells. It has become evident that lymphocytes migrate in a non-random and highly dynamic fashion determined by a range of specific and non-specific factors; in the setting of organ transplantation, patterns are profoundly affected by the interrelated cellular and humoral components of the immunological cascade which may lead either to graft rejection or to its prolongation in untreated and immunologically modified recipients, respectively. Thus, the traffic of lymphocytes throughout host lymphoid and non-lymphoid compartments and their activity within these compartments should be considered an integral part of the host immunomodulation triggered by transplantation of histoincompatible tissue. Gradual filling of the gaps in our current knowledge on the mechanistic aspects of this phenomenon will not only contribute to basic science itself, but also should lead to the development of innovative therapeutic approaches to treat graft rejection.

Rejection of peritubular capillaries in renal allo‐ and xeno‐grafts

“…The only site of entry of leukocytes into rejecting kidney allo‐grafts is via the PTC [20,29]. In lymphoid tissue, high endothelial venules (also referred to as post‐capillary venules), lined by characteristic plump high endothelium, are the entry site for leukocytes into the lymph node [30–32]. In acute cellular rejection, the PTC endothelium can develop features similar to high endothelium [20,21], characterized by typically activated features such as increased cell volume, increased cellular organelles, loss of fenestration, and increased adherence and passage of lymphocytes.…”

Effect of FTY720 and Ex Vivo Graft Irradiation in Rat Small Bowel Transplantation: Expression of Mucosal Addressin Cell Adhesion Molecule-1

“…6 The graft endothelium expresses intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) adhesion molecules, which appear to play a critical role in lymphocyte entry. 7,8 Since among the adhesion molecules, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mediates lymphocytes homing to gut-associated tissues (GALT), it is thus likely to maintain lymphocyte traffi cking during intestinal transplantation. In this study, we performed an analysis of the effect of FTY720 and ex vivo graft irradiation on the graft survival and a semi-quantitative analysis of the MAdCAM-1 expression during small bowel graft rejection in order to assess its involvement in lymphocyte traffi cking to intestinal transplants.…”

Homing of In Vitro-Generated Donor Antigen-Reactive CD4+ T Lymphocytes to Renal Allografts Is α4β1 But Not αLβ2 Integrin Dependent

“…Ag-activated and naive T lymphocytes exhibit distinct in vivo recirculation and homing patterns (3,20,23). Although these differences may not be absolute, activated cells have a higher potential to transmigrate and accumulate at local inflamed tissues, whereas naive T lymphocytes recirculate between peripheral lymphatic compartments.…”

“…Homing of donor Ag-specific T lymphocytes to organ allografts is a complex and highly regulated process (20,23). It depends on the complementary interactions between endothelial cells, lymphocyte surface molecules, and local ECM proteins.…”

“…The use of in vitro preactivated T cells for in vivo homing studies circumvents this problem. Moreover, the ability of resting cells to sequester at the graft site is limited as compared with that of alloactivated cells (20).…”