Mouse CD99 participates in T-cell recruitment into inflamed skin.
Human CD99 is a small highly O-glycosylated cell-surface protein expressed on most leukocytes. It was recently found to be expressed at endothelial cell contacts and to participate in the transendothelial migration (TEM) of monocytes in vitro. In order to analyze the physiologic relevance of CD99 in vivo we searched for the mouse homolog. We cloned a mouse cDNA coding for a protein 45% identical in its sequence with human CD99. Based on the cDNA, we generated antibodies against this mouse homolog of CD99, which detected the antigen on most leukocytes, on endothelia of various tissues, and at cell contacts of cultured endothelial cells. Cell aggregation of CD99-transfected Chinese hamster ovary (CHO) cells was completely blocked by anti-CD99 antibodies. The same antibodies inhibited TEM of lymphocytes in vitro, independent of whether T cells or endothelial cells were preincubated with antibodies. In a cutaneous delayed-type hypersensitivity (DTH) reaction, anti-CD99 antibodies inhibited the recruitment of in vivo-activated T cells into inflamed skin as well as edema formation. We conclude that mouse CD99 participates in the TEM of lymphocytes and in their recruitment to inflamed skin in vivo. This establishes CD99 as a valid target for interference with cutaneous inflammatory processes.
Bixel
Gabriele
G
Max-Planck-Institute of Molecular Biomedicine, Von-Esmarch-Str 56, D-48149 Münster, Germany.
Kloep
Stephan
S
Butz
Stefan
S
Petri
Björn
B
Engelhardt
Britta
B
Vestweber
Dietmar
D
D000071443:12E7 Antigen; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D003001:Cloning, Molecular; D006224:Cricetinae; D003872:Dermatitis / Q000276:immunology / Q000503:physiopathology*; D004487:Edema / Q000276:immunology / Q000503:physiopathology; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D000071443:12E7 Antigen; D000906:Antibodies; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules