Lymphocyte traffic and positioning in vivo: an expanded role for the ECM, the VLA proteins and the cytokines.
The continuous circulation of lymphocytes between blood and lymph, constitutes, with the specific recognition of foreign antigens and with memory, one of the hallmarks of the immunological system. In the routine process of recirculating between blood and lymph in adult life, lymphocytes display the unique capacity of recognizing "self within self". The physiological recognition of "self within self" is expressed at three levels: (1) an overall ability to distinguish between peripheral lymphoid and non-lymphoid organs, (2) the ability of lymphocyte subpopulations to discriminate between peripheral lymphoid organs, (3) a fine recognition of distinct microenvironments within the peripheral lymphoid organs. Historically, interest in regulation of entry into the lymph dominated this field, focusing primarily on the interaction of lymphocytes with post-capillary venules with high endothelium found in some higher vertebrate lymph nodes. Lymphocytes, however, enter the lymph in species without lymph nodes, and lymphocytes recirculation is well established in fetal life. Regardless of route of entry, lymphocytes in birds, fish, rodents, and humans enter the peripheral lymphoid organs and display the capacity to segregate and arrange themselves in distinct territories, a phenomenon called "ecotaxis". This paper reviews the evidence for the relative contribution of so called specialized lymphocyte endothelium interactions and other interactions, to the physiological regulation of lymphocyte traffic and positioning. Of the latter, interactions of lymphocytes with the ECM appear of some significance for two reasons: there is a selective distribution of some ECM components in peripheral lymphoid organ areas, as recently shown for tenascin in the thymus-dependent zones (Chilosi et al., Am J Pathol 143: 1348-1355, 1993). This selective distribution may serve as a basis for preferential T cell migration through those zones. The abnormal expression of tenascin in non-lymphoid organs with autoimmune lesions may serve as an identical basis for abnormal T lymphocyte migration in autoimmunity (Chilosi, personal communication). Additional evidence for abnormal cell-ECM interactions playing a role in autoimmune-like lesions comes from the recent observations in TGF-beta 1 knockout mice, in which mononuclear cell infiltration of the heart and lungs has been corrected by the systemic administration of synthetic FN peptides (Hines at al., PNAS 91:5187-5191, 1994). Changes in expression of ECM components have aso being described in rat heart allografts preceding lymphocyte accumulation in the process of allograft rejection (Coito et atl. Transplantation 57:599-605, 1994).(ABSTRACT TRUNCATED AT 400 WORDS)
de Sousa
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Abel Salazar Institute for the Biomedical Sciences, Oporto, Portugal.
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004729:Endothelium, Lymphatic / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000502:physiology*
D016207:Cytokines; D016029:Receptors, Very Late Antigen