Endothelial antigen presentation: stimulation of previously activated but not naïve TCR-transgenic mouse T cells.
In vitro experiments have shown that endothelial cells can function as antigen-presenting cells to CD4(+) T lymphocytes. The studies presented here address the question of whether naïve versus previously activated CD4(+) helper T cells differ in their responses to endothelial antigen presentation. TCR-transgenic mice were used as a source of naive T cells of defined antigen specificity. These cells were stimulated in vitro with antigen and splenic antigen-presenting cells to generate populations of T lymphocytes with a previously activated/memory phenotype. Two different types of mouse endothelial cells were used as antigen-presenting cells, including the SVEC4-10 line derived from lymph node endothelium and primary murine pulmonary microvascular endothelium. Monolayer cultures of both types of endothelium were capable of antigen-dependent stimulation of previously activated TCR-transgenic CD4(+) cells. In contrast, neither endothelial type could activate naïve CD4(+) T cells. When costimulatory signals were provided in trans by the addition of MHC-mismatched mouse spleen cells, activation of naïve T cells by endothelial antigen presentation could be demonstrated. The expression of ICAM-1 or VCAM-1 on the endothelial cells was not sufficient to activate naïve T cells. Furthermore, the mouse lung endothelium constitutively expresses B7-1, and therefore, the inability of endothelium to stimulate naïve T cells could not be attributed to a lack of CD28-ligands. These studies suggest that the potential role of endothelial antigen presentation in immune responses is restricted to promoting responses by T cells which have previously encountered antigen presented by other antigen-presenting cells.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, 02114, USA.
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VL
Perez
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Henault
A H
AH
Lichtman
D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000276:immunology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018122:B7-1 Antigen; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1