Subset-Specific Reductions in Lung Lymphocyte Accumulation Following Intratracheal Antigen Challenge in Endothelial Selectin-Deficient Mice

Abstract

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 ∼60% early, but equivalent to wt levels later. Surprisingly, many γδ 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 αβ 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 αβ 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.

CCR2 and CCR6, but Not Endothelial Selectins, Mediate the Accumulation of Immature Dendritic Cells within the Lungs of Mice in Response to Particulate Antigen

“…Thus, lung DC appear to migrate to lung tissue during inflammation in an endothelial selectin-independent fashion, in contrast to the case in the inflamed skin (15). Analysis of identically treated E Ϫ P Ϫ mice showed reductions in numbers of CD4 ϩ , CD8 ϩ , and CD19 ϩ cell in both lung mince and BAL that were very similar to those we have described previously (data not shown) (32).…”

“…challenge (27) and have shown that endothelial selectins are required for recruitment to the lungs of some lymphocyte subsets (B cells and CD8 cells at all time points, and CD4 cells early after i.t. challenge) (30,32). However, because absence of endothelial selectins does not reduce recruitment of granulocytes or total mononuclear phagocytes, nor impair the ability to prime lymphocytes via the i.p.…”

“…This model was chosen for its ability to induce an acute, self-limited inflammatory response with a clearly definable onset and well-established kinetics. Previous studies have proven this model system useful in defining the molecular mechanisms of lung leukocyte recruitment (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Following i.t.…”

“…The first were the endothelial selectins, E-selectin (CD62E) and P-selectin (CD62P). In this model system, the endothelial selectins are markedly up-regulated (27) and are essential for recruitment of some lymphocyte subsets (30,32). iDC bind E-and P-selectins under shear stress (15), making this adhesive system a plausible requirement for their recruitment.…”

Selectin Ligand-Independent Priming and Maintenance of T Cell Immunity during Airborne Tuberculosis

“…Few studies, however, also report on impaired leukocyte extravasation into peripheral organs (39,45). In endothelial E-and P-selectin-deficient mice that have been intratracheally primed and challenged with SRBCs, a similar, only delayed CD4 ϩ T cell infiltration into the lungs was observed, suggesting that selectins do not seem to play an important role in T cell homing to the lungs (46). With respect to mycobacterial infections, at least P-selectin has been shown to be dispensable for leukocyte recruitment and granuloma formation (47).…”