Low percentages of circulating CD8(+)/CD45RA(+) human T lymphocytes expressing beta7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the alpha4beta7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, alpha4beta7(+) donor T cells. Therefore, we evaluated the correlation existing between circulating beta7(+) T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD.


METHODS
Surface expression of beta7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD.


RESULTS
We found a significantly higher absolute number of CD8(+) and a significantly lower percentage of CD8(+)CD45RA(+)beta7(+) T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8(+) T cells > or = 60 x 10(6)/L and a percentage of circulating CD8(+)CD45RA(+)beta7(+) T cells < 35%.


CONCLUSIONS
Measuring the absolute number of CD8(+) T cells and percentage of CD8(+)CD45RA(+)beta7(+) T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.
Avanzini
M Antonietta
MA
Pediatric Hematology-Oncology and Laboratory of Transplant Immunology, IRCCS Policlinico San Matteo-Pavia, University of Pavia, Pavia, Italy.
Maccario
Rita
R
Locatelli
Franco
F
Giebel
Sebastian
S
Santos
Conceiçao Dos
CD
Bernardo
Maria Ester
ME
Pagliara
Daria
D
Montagna
Daniela
D
Longo
Stefania
S
Amendola
Giovanni
G
Marconi
Massimo
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D039641:Integrin beta Chains / Q000096:biosynthesis / Q000097:blood*; D016023:Integrins / Q000096:biosynthesis / Q000097:blood*; D007410:Intestinal Diseases / Q000097:blood* / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count / Q000379:methods; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000628:therapy; D014184:Transplantation, Homologous
D015415:Biomarkers; D039641:Integrin beta Chains; D016023:Integrins; C071777:integrin alpha4beta7; C091368:integrin beta7