Trafficking pathways and characterization of CD4 and CD8 cells recruited to the skin of humans experimentally infected with Haemophilus ducreyi.
T-cell homing to infected skin is not well studied in humans. We examined sites experimentally infected with Haemophilus ducreyi by immunohistochemistry and flow cytometry for expression of receptors and ligands involved in cutaneous T-cell homing and determined the phenotypes of the T cells that trafficked to skin. Endothelial cells expressed E-selectin in infected but not uninfected skin, while peripheral node addressin (PNAd) was minimally expressed in all samples. CC chemokine ligand 27 (CCL27) was expressed in the epidermis and endothelium of both infected and uninfected skin. Interestingly, CCL21, a chemokine thought to be associated principally with T-cell trafficking in the lymphatic compartment, was highly expressed on the endothelium of infected skin. Few naive cells were present in experimental lesions, emphasizing the combined role of PNAd and CCL21 in trafficking of this subset. Memory cells (CD45RA-) dominated both CD4 and CD8 T-cell populations at the site of infection. Effector memory (CD45RA- CD27-) CD4+ and CD8+ T cells were enriched in lesions. Although the CC chemokine receptor 7-positive (CCR7+) population of both central memory (CD45RA- CD27+) and effector memory cells was not enriched in the skin compared to peripheral blood, CCR7+ cells were not precluded from entering infected skin. Taken together with our previous work (D. Soler, T. L. Humphreys, S. M. Spinola, and J. J. Campbell, Blood 101:1677-1683, 2003), these studies led us to propose a model of memory T-cell trafficking to skin in response to experimental H. ducreyi infection.
Department of Medicine, Indiana University, Indianapolis, Indiana 46202, USA. trhumphr@iupui.edu
Tricia L
TL
Humphreys
Lee Ann
LA
Baldridge
Steven D
SD
Billings
James J
JJ
Campbell
Stanley M
SM
Spinola
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement; D002602:Chancroid / Q000276:immunology*; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D012867:Skin / Q000276:immunology*
C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine