Altered homeostasis of CD4(+) memory T cells in allogeneic hematopoietic stem cell transplant recipients: chronic graft-versus-host disease enhances T cell differentiation and exhausts central memory T cell pool.
An increased risk of late infection is a serious complication after allogeneic hematopoietic stem cell transplantation (AHSCT), especially for recipients with defective CD4(+) T cell recovery. Although chronic graft-versus-host disease (cGVHD) negatively influences CD4(+) T cell reconstitution, the mechanisms leading to this defect are not well understood. We found that the proportion of CD27(-) CD4(+) T cells was remarkably increased in ASHCT recipients with cGVHD or with repetitive infectious episodes. Isolated CD27(-) CD4(+) T cells from ASHCT recipients had significantly shortened telomere length, displayed enhanced vulnerability to activation-induced cell death, and showed extremely reduced clonal diversity, when compared with CD27(-) CD4(+) T cells from healthy donors. Also, CD27(+) CD4(+) T cells from AHSCT recipients easily lost their expression of CD27 in response to antigen stimulation regardless of cGVHD status. Taken together, these data indicate that homeostasis of memory CD4(+) T cells from AHSCT recipients is altered, and that they easily transit into CD27(-) effector memory T cells. Increased in vivo T cell stimulation observed in recipients with cGVHD further promotes the transition to effector memory cells, a change that decreases the central memory CD4(+) T cell pool and consequently weakens the recipient's defense against persistently infecting pathogens.
Fukunaga
Akiko
A
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ishikawa
Takayuki
T
Kishihata
Masako
M
Shindo
Takero
T
Hori
Toshiyuki
T
Uchiyama
Takashi
T
D000328:Adult; D000368:Aged; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D015415:Biomarkers; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7