Subset-specific reductions in lung lymphocyte accumulation following intratracheal antigen challenge in endothelial selectin-deficient mice.
We previously demonstrated induction and expression of CD62E and CD62P in the lungs of mice primed and then challenged with intratracheal (i.t.) SRBC. The current study examined accumulation of endogenous lymphocytes in the lungs of endothelial E- and P-selectin-deficient (E(-)P(-)) mice after i.t. SRBC challenge. Compared with syngeneic wild-type (wt) mice, E(-)P(-) mice showed an 85-95% decrease in CD8(+) T cells and B cells in the lungs at both early and late time points. In contrast, CD4(+) T cell accumulation was reduced by approximately 60% early, but equivalent to wt levels later. Surprisingly, many gammadelta T cells were found in lungs and blood of E(-)P(-) mice but were undetectable in the lungs and blood of wt mice. Absolute numbers of peripheral blood CD4, CD8, and B lymphocytes in E(-)P(-) mice equaled or exceeded the levels in wt mice, particularly after challenge. Trafficking studies using alphabeta T lymphoblasts confirmed that the recruitment of circulating cells after challenge was markedly reduced in E(-)P(-) mice. Furthermore, Ag priming occurred normally in both the selectin-deficient and wt mice, because primed lymphocytes from both groups transferred Ag sensitivity into naive wt mice. Lung production of mRNA for six CC and two CXC chemokines after challenge was equivalent by RT-PCR analysis in wt and E(-)P(-) mice. Therefore, reduced lung accumulation of alphabeta T cells and B cells in E(-)P(-) mice did not result from reduced delivery of circulating lymphocytes to the lungs, unsuccessful Ag priming, or defective pulmonary chemokine production. Selectin-dependent lymphocyte recruitment into the lungs following i.t.-SRBC challenge is subset specific and time dependent.
Curtis
Jeffrey L
JL
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health Care System, Ann Arbor 48109, USA. jlcurtis@umich.edu
Sonstein
Joanne
J
Craig
Ronald A
RA
Todt
Jill C
JC
Knibbs
Randall N
RN
Polak
Timothy
T
Bullard
Daniel C
DC
Stoolman
Lloyd M
LM
D019264:Adoptive Transfer; D000818:Animals; D001789:Blood Group Antigens / Q000008:administration & dosage* / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D019742:Chemokines, CC / Q000096:biosynthesis; D019743:Chemokines, CXC; D019040:E-Selectin / Q000235:genetics* / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D007442:Intubation, Intratracheal; D008168:Lung / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D008218:Lymphocytosis / Q000097:blood / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000502:physiology; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology
D001789:Blood Group Antigens; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019040:E-Selectin; D019007:P-Selectin