Severe chronic graft-versus-host disease is characterized by a preponderance of CD4(+) effector memory cells relative to central memory cells.
Donor alloreactive CD4(+) T cells are important to the pathogenesis of chronic graft-versus-host disease (cGVHD), but specific subsets of CD4(+) T cells responsible for GVHD have not been defined. We hypothesized that cGVHD might be associated with a preponderance of CD4(+) effector memory cells (CCR7(-)/CD62L(low), CD4(EM)). We analyzed CCR7 and CD62L expression on CD4(+) T cells from stem cell transplantation patients, who did or did not develop cGVHD, and healthy donors. Patients with cGVHD had a higher percentage of CD4(EM) cells (35.5% +/- 2.9%) than healthy donors (13.8% +/- 0.7%; P <.0001) or patients without cGVHD that received a transplant (21.7% +/- 2.1%; P <.01). Using corticosteroid dose as a surrogate marker for cGVHD severity, severe cGVHD was associated with a higher percentage of CD4(EM) cells. The proportion of CD4(EM) cells in corticosteroid-dependent patients with systemic lupus erythematosis or Wegener granulomatosis did not differ from patients without cGVHD that received a transplant. This finding implies that overrepresentation of CD4(EM) cells is a unique feature of cGVHD.
Yamashita
Kouhei
K
Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-1886, USA. kyamashita@niaid.nih.gov
Choi
Uimook
U
Woltz
Patricia C
PC
Foster
Susan F
SF
Sneller
Michael C
MC
Hakim
Francis T
FT
Fowler
Daniel H
DH
Bishop
Michael R
MR
Pavletic
Steven Z
SZ
Tamari
Marisa
M
Castro
Kathleen
K
Barrett
A John
AJ
Childs
Richard W
RW
Illei
Gabor G
GG
Leitman
Susan F
SF
Malech
Harry L
HL
Horwitz
Mitchell E
ME
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002908:Chronic Disease; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019041:L-Selectin / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin