The in vivo behavior of T cell clones: altered migration due to loss of the lymphocyte surface homing receptor.
Although cloned lines of T lymphocytes have been valuable in defining the in vitro functions of well-defined cell types, they have often demonstrated relatively poor activity in vivo. One striking property of T cells clones which might affect their in vivo activity is their unusual inability to localized in lymphoid tissue as do most normal T cells. Normal lymphocyte recirculation and localization requires that lymphocytes recognize and pass through the walls of specialized high endothelial venules (HEV) as they enter into lymph nodes. We previously showed that murine T cell clones are unable to home into the peripheral lymphoid organs-lymph nodes and Peyer's patches. The inability of these cells to recognize lymph node HEV in an in vitro frozen section adherence assay suggested that the lack of lymphoid homing was due to the loss of a normal lymphocyte surface receptor for HEV. The present experiments were designed to determine: 1) the molecular mechanism responsible for the loss of normal lymphocyte migration, and 2) whether these migration and homing characteristics are irreversible features of T cell clones. Flow cytometric analysis of helper and cytolytic clones using a monoclonal antibody (MEL-14) specific for the lymphocyte homing receptor showed that they lack this surface receptor. This lack of receptor expression was confirmed by the inability to detect the antigen in detergent-solubilized extracts of surface-radiolabeled cells. Thus, the lack of homing to lymph nodes appears to be due to the loss of expression of the surface receptor which mediates the interaction between lymphocytes and HEV. When clones were rested in vitro in a nonproliferative state without stimulation by antigen or growth factors, they did not regain expression of the surface homing receptor or the ability to migrate to lymph nodes in vivo. The lack of receptor expression, therefore, is not merely associated with a rapidly proliferating state, but rather seems to be an irreversible feature of T cell clones, at least under in vitro culture conditions. T cell clones, both rested and recently restimulated, share certain features characteristic of activated T cells, as shown by recent results with MLC-stimulated T cell blasts. Both populations are large, brightly PNA-positive lymphocytes which lack expression of the MEL-14 receptor and do not home to peripheral lymphoid tissue. We propose that this PNA-high, MEL-14- nonrecirculating phenotype may represent a normal phase of T cell differentiation through which many T cells pass after being activated by specific antigen.(ABSTRACT TRUNCATED AT 400 WORDS)
Dailey
M O
MO
Department of Pathology, Stanford University School of Medicine, CA 94305.
Gallatin
W M
WM
Weissman
I L
IL
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000172:deficiency*; D016201:Receptors, Lymphocyte Homing; D013156:Splenectomy; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology
D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing