T cells recognize intravascular
antigen presented by patrolling monocytes
Clare L.V. Westhorpe
, M. Ursula Norman
, Pam Hall
, Sarah L. Snelgrove
, Michaela Finsterbusch
, Anqi Li
, Zhe Hao Tan
, Songhui Li
, Susan K. Nilsson
, A. Richard Kitching
Michael J. Hickey
Although effector CD4
T cells readily respond to antigen outside the vasculature, how they
respond to intravascular antigens is unknown. Here we show the process of intravascular
antigen recognition using intravital multiphoton microscopy of glomeruli. CD4
undergo intravascular migration within uninﬂamed glomeruli. Similarly, while MHCII is not
expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol
glomerular capillaries, interacting with CD4
T cells. Following intravascular deposition of
antigen in glomeruli, effector CD4
T-cell responses, including NFAT1 nuclear translocation
and decreased migration, are consistent with antigen recognition. Of the MHCII
cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations.
These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion
T-cell-dependent glomerular inﬂammation. These ﬁndings indicate that
monocytes patrolling the glomerular microvasculature can present intravascular
antigen to CD4
T cells within glomerular capillaries, leading to antigen-dependent
Centre for Inﬂammatory Diseases, Monash University Department of Medicine Monash Medical Centre, 246 Clayton Rd., Clayton, VIC 3168, Australia.
Monash Micro Imaging, Monash University, Wellington Rd., Clayton, VIC 3800, Australia.
Biomedical Manufacturing, CSIRO Manufacturing, Bag 10,
Clayton South, VIC 3169, Australia.
Australian Regenerative Medicine Institute, Monash University, Wellington Rd., Clayton, VIC 3800, Australia.
Departments of Nephrology and Pediatric Nephrology, Monash Medical Centre, 246 Clayton Rd., Clayton, VIC 3168, Australia.
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstr. 17, 1090 Vienna, Austria. Clare L.V. Westhorpe
and M. Ursula Norman contributed equally to this work. Correspondence and requests for materials should be addressed to
M.J.H. (email: firstname.lastname@example.org)