Effector and suppressor roles for LFA-1 during the development of experimental autoimmune encephalomyelitis.
LFA-1 (CD11a/CD18) is a member of the beta(2)-integrin family of adhesion molecules important in leukocyte trafficking and activation. Although LFA-1 is thought to contribute to the development of experimental autoimmune encephalomyelitis (EAE) primarily through its functions on effector T cells, its importance on other leukocyte populations remains unexplored. To address this question, we performed both adoptive transfer EAE experiments involving CD11a(-/-) mice and trafficking studies using bioluminescent T cells expressing luciferase under the control of a CD2 promoter (T-lux cells). Transfer of encephalitogenic CD11a(-/-) T cells to wild type mice resulted in a significant reduction in overall EAE severity compared to control transfers. We also observed, using in vivo imaging techniques, that CD11a(-/-) T-lux cells readily infiltrated lymph nodes and the CNS of wild type recipients with kinetics comparable to CD11a(+/+) transfers, although their overall numbers in these organs were reduced. Surprisingly, transfer of encephalitogenic wild type T cells to CD11a(-/-) mice induced a severe and sometimes fatal EAE disease course, associated with massive T cell infiltration and proliferation in the CNS. These data indicate that LFA-1 expression on leukocytes in recipient mice plays an important immunomodulatory role in EAE. Thus, LFA-1 acts as a key regulatory adhesion molecule during the development of EAE, serving both pro- and anti-inflammatory roles in disease pathogenesis.
Dugger
Kari J
KJ
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Zinn
Kurt R
KR
Weaver
Casey
C
Bullard
Daniel C
DC
Barnum
Scott R
SR
D000704:Analysis of Variance; D000818:Animals; D040881:CD11a Antigen / Q000235:genetics; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D006023:Glycoproteins / Q000009:adverse effects; D008156:Luciferases / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000009:adverse effects; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors
D040881:CD11a Antigen; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D008156:Luciferases