The Journal of Immunology, Vol 149, Issue 10 3394-3402, Copyright © 1992 by American Association of Immunologists

ARTICLES

Inhibition of lymphocyte endothelial adhesion and in vivo lymphocyte migration to cutaneous inflammation by TA-3, a new monoclonal antibody to rat LFA-1

TB Issekutz
Department of Pediatrics, Dalhousie University, Izaak Walton Killam Hospital for Children, Halifax, Nova Scotia, Canada.

Lymphocyte function-associated Ag-1 (LFA-1) or CD11a/CD18 mediates lymphocyte adhesion to cultured vascular endothelial cells (EC). Thus, LFA-1 likely plays a major role in lymphocyte migration out of the blood, but there is little information on this in vivo. Small peritoneal exudate lymphocytes (sPEL) and lymph node (LN) lymphoblasts adhere to cytokine-activated EC and preferentially migrate to cutaneous inflammatory sites. The role of LFA-1 in the adherence and in vivo migration of these T cells was determined. Because of a lack of anti- rat LFA-1, mAb were prepared to rat T cells. One mAb, TA-3, inhibited homotypic aggregation; T cell proliferation to Ag, alloantigens, and mitogens; stained all leukocytes; and immunoprecipitated 170- and 95- kDa polypeptides from lymphocytes and neutrophils. TA-3 binding to lymphocytes also required Ca2+, but not Mg2+. Thus, TA-3 appears to react with rat LFA-1. TA-3 inhibited spleen T cell adhesion to unstimulated EC by 30% and to IFN-gamma, TNF-alpha, IL-1 alpha, and LPS stimulated EC by 50 to 60% but inhibited sPEL EC adhesion by only 10%. TA-3 also strongly inhibited anti-CD3-stimulated LN T cell adherence. The migration of spleen T cells to delayed-type hypersensitivity and skin sites injected with LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF was inhibited by 72 to 88% by TA-3, and was decreased by 50% to peripheral LN. TA-3 caused less but still 50 to 60% inhibition of sPEL migration to inflamed skin. Lymphoblast migration to skin was inhibited 40 to 80% and to PLN by 30%. Migration of lymphocytes from all sources to mesenteric LN was inhibited by 32 to 60%. In conclusion, LFA-1 mediates much of the adherence of spleen T cells and lymphoblasts to EC in vitro, most of the migration of these cells to dermal inflammation and about 50% of the homing of LN and spleen T cells to peripheral and mesenteric LN. sPEL are less dependent on LFA-1 for adhesion to EC in vitro and for migration to inflamed skin and LN in vivo.

This article has been cited by other articles:

				K. Mohan and T. B. Issekutz Blockade of Chemokine Receptor CXCR3 Inhibits T Cell Recruitment to Inflamed Joints and Decreases the Severity of Adjuvant Arthritis J. Immunol., December 15, 2007; 179(12): 8463 - 8469. [Abstract] [Full Text] [PDF]

				S. I. Zittermann and A. C. Issekutz Endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation J. Leukoc. Biol., August 1, 2006; 80(2): 247 - 257. [Abstract] [Full Text] [PDF]

				S. I. Zittermann and A. C. Issekutz Basic Fibroblast Growth Factor (bFGF, FGF-2) Potentiates Leukocyte Recruitment to Inflammation by Enhancing Endothelial Adhesion Molecule Expression Am. J. Pathol., March 1, 2006; 168(3): 835 - 846. [Abstract] [Full Text] [PDF]

				I. Cvetkovic, Y. Al-Abed, D. Miljkovic, D. Maksimovic-Ivanic, J. Roth, M. Bacher, H. Y. Lan, F. Nicoletti, and S. Stosic-Grujicic Critical Role of Macrophage Migration Inhibitory Factor Activity in Experimental Autoimmune Diabetes Endocrinology, July 1, 2005; 146(7): 2942 - 2951. [Abstract] [Full Text] [PDF]

				J. C. U. Lehmann, D. Jablonski-Westrich, U. Haubold, J.-C. Gutierrez-Ramos, T. Springer, and A. Hamann Overlapping and Selective Roles of Endothelial Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 in Lymphocyte Trafficking J. Immunol., September 1, 2003; 171(5): 2588 - 2593. [Abstract] [Full Text] [PDF]

				K. Mohan, Z. Ding, J. Hanly, and T. B. Issekutz IFN-{gamma}-Inducible T Cell {alpha} Chemoattractant Is a Potent Stimulator of Normal Human Blood T Lymphocyte Transendothelial Migration: Differential Regulation by IFN-{gamma} and TNF-{alpha} J. Immunol., June 15, 2002; 168(12): 6420 - 6428. [Abstract] [Full Text] [PDF]

				A W Stadnyk, C Dollard, T B Issekutz, and A C Issekutz Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent Gut, May 1, 2002; 50(5): 629 - 635. [Abstract] [Full Text] [PDF]

				A. C. Issekutz and T. B. Issekutz The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation J. Immunol., February 15, 2002; 168(4): 1934 - 1939. [Abstract] [Full Text] [PDF]

				S. Kanwar, C. W. Smith, F. R. Shardonofsky, and A. R. Burns The Role of Mac-1 (CD11b/CD18) in Antigen-Induced Airway Eosinophilia in Mice Am. J. Respir. Cell Mol. Biol., August 1, 2001; 25(2): 170 - 177. [Abstract] [Full Text] [PDF]

				C. Faveeuw, M. E. Di Mauro, A. A. Price, and A. Ager Roles of {alpha}4 integrins/VCAM-1 and LFA-1/ICAM-1 in the binding and transendothelial migration of T lymphocytes and T lymphoblasts across high endothelial venules Int. Immunol., March 1, 2000; 12(3): 241 - 251. [Abstract] [Full Text] [PDF]

				U. Birner, T. B. Issekutz, U. Walter, and A. C. Issekutz The role of {alpha}4 and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis Int. Immunol., February 1, 2000; 12(2): 141 - 150. [Abstract] [Full Text] [PDF]

				C. G. Feng, A. G. D. Bean, H. Hooi, H. Briscoe, and W. J. Britton Increase in Gamma Interferon-Secreting CD8+, as Well as CD4+, T Cells in Lungs following Aerosol Infection with Mycobacterium tuberculosis Infect. Immun., July 1, 1999; 67(7): 3242 - 3247. [Abstract] [Full Text] [PDF]