title: CD11a is essential for normal development of hematopoietic intermediates.
abstract: The process of lymphopoiesis begins in the bone marrow (BM) and requires multiple cellular intermediates. For T cell production, lymphoid progenitors exit the BM and home to the thymus where maturation and selection ensue. These processes are dependent on a number of factors, including chemokines and adhesion molecules. Although the β2 integrin CD11a plays an important role in the migration of lymphocytes to lymph nodes, the role of CD11a in T cell development is largely undefined. Our studies now show that, in CD11a(-/-) mice, thymic cellularity was decreased and early T cell development was partially impaired. Remarkably, CD11a was critical for generation of common lymphoid progenitors (CLPs) and lymphoid-primed multipotent progenitors. However, in intact CD11a(-/-) mice, peripheral B and T cell subsets were only modestly altered, suggesting that compensatory mechanisms were operating. In contrast, competitive BM-reconstitution assays revealed an essential role for CD11a in the generation of thymocytes and mature T and B cells. This defect was linked to the requirement for CD11a in the development of CLPs. Furthermore, our results identified CLPs, and not lymphoid-primed multipotent progenitors, as the requisite CD11a-dependent precursor for lymphocyte development. Thus, these findings established a key role for CD11a in lymphopoiesis.
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Tina O
authors.initials: TO
authors.lastname: Bose
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030 puddington@uchc.edu colpitts@uchc.edu.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Colpitts
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Quynh-Mai
authors.initials: QM
authors.lastname: Pham
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030 puddington@uchc.edu colpitts@uchc.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Puddington
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D040881:CD11a Antigen / Q000235:genetics*; D019070:Cell Lineage; D015870:Gene Expression; D054503:Lymphoid Progenitor Cells / Q000276:immunology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D040881:CD11a Antigen
references.citation: Development. 2011 Mar;138(6):1017-31
references.pmid: 21343360
references.citation: Cell Res. 2006 Feb;16(2):189-95
references.pmid: 16474433
references.citation: Eur J Immunol. 2005 Jul;35(7):2019-30
references.pmid: 15971276
references.citation: J Immunol. 1991 Nov 1;147(9):2852-9
references.pmid: 1680920
references.citation: PLoS Biol. 2004 Mar;2(3):E75
references.pmid: 15024423
references.citation: J Exp Med. 1996 Apr 1;183(4):1415-26
references.pmid: 8666900
references.citation: Blood. 2006 Oct 15;108(8):2531-9
references.pmid: 16809609
references.citation: J Immunol. 2007 Feb 15;178(4):2008-17
references.pmid: 17277104
references.citation: Science. 2009 Apr 17;324(5925):392-7
references.pmid: 19286519
references.citation: Nat Immunol. 2004 Sep;5(9):953-60
references.pmid: 15300246
references.citation: Nat Immunol. 2007 Nov;8(11):1207-16
references.pmid: 17922016
references.citation: Blood. 2010 Feb 11;115(6):1137-44
references.pmid: 20009033
references.citation: Genes Dev. 2009 Oct 15;23(20):2376-81
references.pmid: 19833765
references.citation: Infect Immun. 2013 Apr;81(4):1140-51
references.pmid: 23357382
references.citation: Blood. 2011 Aug 18;118(7):1962-70
references.pmid: 21659540
references.citation: J Exp Med. 1994 Nov 1;180(5):1955-60
references.pmid: 7964471
references.citation: J Immunol. 1996 Dec 15;157(12):5375-86
references.pmid: 8955185
references.citation: Exp Hematol. 2008 Sep;36(9):1143-1156
references.pmid: 18718416
references.citation: Cell. 2005 Apr 22;121(2):295-306
references.pmid: 15851035
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7006-11
references.pmid: 16641096
references.citation: Immunity. 2001 Oct;15(4):659-69
references.pmid: 11672547
references.citation: J Exp Med. 1993 Oct 1;178(4):1283-92
references.pmid: 7690832
references.citation: Immunology. 1997 Apr;90(4):550-6
references.pmid: 9176108
references.citation: Nat Immunol. 2005 Jun;6(6):626-34
references.pmid: 15880112
references.citation: Cell. 1997 Nov 28;91(5):661-72
references.pmid: 9393859
references.citation: Immunity. 2002 Dec;17(6):749-56
references.pmid: 12479821
references.citation: Nat Commun. 2012;3:1098
references.pmid: 23033074
references.citation: Cold Spring Harb Protoc. 2009 Feb;2009(2):pdb.prot5156
references.pmid: 20147086
references.citation: Eur J Immunol. 1996 Sep;26(9):2050-5
references.pmid: 8814245
references.citation: Cell. 1994 Jan 28;76(2):301-14
references.pmid: 7507411
references.citation: Cell Immunol. 1996 May 25;170(1):11-9
references.pmid: 8660794
references.citation: Science. 2006 Jan 6;311(5757):83-7
references.pmid: 16322423
references.citation: Blood. 2001 Mar 1;97(5):1282-8
references.pmid: 11222371
references.citation: Blood. 2010 Mar 11;115(10):1897-905
references.pmid: 19965655
references.citation: Annu Rev Immunol. 1992;10:759-83
references.pmid: 1375474
references.citation: Science. 2001 Nov 30;294(5548):1933-6
references.pmid: 11729320
references.citation: Blood. 2010 Mar 11;115(10):1906-12
references.pmid: 20040757
references.citation: Immunity. 2002 Aug;17(2):117-30
references.pmid: 12196284
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14541-6
references.pmid: 11724967
references.citation: Ann N Y Acad Sci. 2011 Jan;1217:122-38
references.pmid: 21251013
references.citation: Nat Rev Immunol. 2003 Nov;3(11):859-66
references.pmid: 14668802
references.citation: J Exp Med. 2003 Nov 17;198(10):1495-506
references.pmid: 14610045
references.citation: Blood. 2002 Jul 1;100(1):327-33
references.pmid: 12070044