Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and CD8+ T cells in vivo.
Intraepithelial lymphocytes (IEL) of the intestinal epithelium represent a phenotypically and functionally distinct subpopulation of peripheral T cells. In this study, we report the production of a mAb, designated HL3, which exhibits reactivity with a subset of IEL. In differential screening assays HL3 reacted with 30 to 50% of IEL, but not with T cells of the thymus, spleen, or lymph nodes. Biochemical characterization revealed that the HL3 mAb recognized p150,95 (CD11c/CD18; CR4), a member of the beta 2-integrin family. Fluorescence flow cytometric analyses showed that p150,95 was expressed by TCR-alpha beta or TCR-gamma delta CD4-8+ IEL but not by CD4+8- IEL. Induction of graft-vs-host (GVH) disease resulted in up-regulation of p150,95 expression on donor-derived CD8+ T cells in the intestinal epithelium, as well as in the spleen and lymph nodes. GVH also induced MAC-1 (CD11b) expression on a subset of CD8+ lymph node T cells, but MAC-1 was not up-regulated on CD8+ IEL in this situation. In contrast, activation of identical T cell responders in vitro resulted in weak induction of p150,95 and MAC-1 expression. This result suggested that activation alone was insufficient for p150,95 up-regulation and that additional factors available in vivo were essential in this process. In the intestine, induction of p150,95 required the presence of intestinal flora as IEL from germfree mice lacked p150,95. Interestingly, gamma delta IEL expressing a non-IEL type transgenic TCR were also p150,95-, but exposure to Ag in vivo, but not in vitro, resulted in p150,95 induction. This result indicated that the constitutive expression of p150,95 on IEL is likely due to Ag stimulation via the TCR and not a bystander phenomenon. Overall, the results demonstrated p150,95 to be a hallmark of T cell activation in vivo and an indicator of ongoing antigen-specific T cell activation in the intestinal epithelium.
Huleatt
J W
JW
Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington 06030, USA.
Lefrançois
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D000911:Antibodies, Monoclonal; D016167:Integrin alphaXbeta2; D011948:Receptors, Antigen, T-Cell