Heterogeneity and biased T cell receptor α/β repertoire of mucosal CD8+ cells from murine large intestine : implications for functional state

• Published in: The Journal of experimental medicine 1994-08, Vol.180 (2), p.433-444
• Main Authors: IBRAGHIMOV, A. R, LYNCH, R. G
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD8 Antigens; Cell Adhesion; Cell Differentiation; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestine, Large - cytology; Intestine, Large - immunology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred Strains; Receptors, Antigen, T-Cell, alpha-beta - immunology; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.180.2.433

Up to 90% of CD8+ intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the alpha/beta T cell lineage and consist of two subsets. One subset expresses both alpha and beta subunits of the CD8 coreceptor, and is uniformly Thy1+, CD5+, B220-, CD2+, CD28+. The CD8 alpha+beta+ LI-IEL exclude self-reacting V beta structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8 alpha+beta- subset of TCR-alpha/beta+ LI-IEL is Thy1-/+, CD5-, B220+, CD2+/-, and CD28-. It contains cells with potentially self-reacting V beta s and is responsive in vivo to high doses of anti-TCR-alpha/beta monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8 alpha+beta+ LI-IEL in nude mice undergo the same V beta deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin alpha M290 beta 7, known to be a homing receptor for IEL. Unusually high proportions of CD69+ cells within both subsets indicate chronic activation. The proportions of CD69+ and alpha M290 beta 7+ cells within the CD8 alpha+beta+ subset increase with age, probably due to constant antigenic challenge. We propose that CD8 alpha+beta+ and CD8 alpha+beta- subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8+ T cells. The CD8 alpha+beta+ undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8 alpha+beta- subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR-mediated stimuli.