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Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant.

Mendes AV, Kallas EG, Benard G, Pannuti CS, Menezes R, Dulley FL, Evans TG, Salomão R, Machado CM - Clinics (Sao Paulo) (2008)

Bottom Line: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients.Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05).This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Virologia, Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. avamendes@gmail.com

ABSTRACT

Objectives: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients.

Methods: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays.

Results: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01) and an increase in CD57+ lymphocytes (5.60%, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05).

Conclusion: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

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Proposed model for CD8+ T lymphocyte subset reconstitution after BMT and the effect of CMV viremia. A continuous relative decrease in CD28+ cells, along with a continuous relative increase in CD57+, takes place after BMT engraftment. The occurrence of CMV viremia exerts a substantial effect on this system, causing a steep incline in both curves
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f4-16-0109: Proposed model for CD8+ T lymphocyte subset reconstitution after BMT and the effect of CMV viremia. A continuous relative decrease in CD28+ cells, along with a continuous relative increase in CD57+, takes place after BMT engraftment. The occurrence of CMV viremia exerts a substantial effect on this system, causing a steep incline in both curves

Mentions: An association between expansion of the CD57+CD8+ T lymphocyte subset and CMV infection in BMT was first suggested by Dolstra et al., who described a higher number of these cells in those patients that developed CMV infection.45 In two patients, CMV-specific cytotoxicity activity was also demonstrated in vitro46. Our findings strongly suggest an association between CMV viremia and the relative expansion of this subset, with an impressive increase of greater than 6% at the time of CMV antigenemia occurrence. The observed temporal association between CMV viremia and the relative increase in the CD57+CD28−CD8+ T lymphocyte subset suggests the presence of an antigen-specific response driven by CMV (Figure 4). However, when patients were divided into allogeneic and autologous BMT groups, we could demonstrate this association only in the allogeneic BMT group.


Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant.

Mendes AV, Kallas EG, Benard G, Pannuti CS, Menezes R, Dulley FL, Evans TG, Salomão R, Machado CM - Clinics (Sao Paulo) (2008)

Proposed model for CD8+ T lymphocyte subset reconstitution after BMT and the effect of CMV viremia. A continuous relative decrease in CD28+ cells, along with a continuous relative increase in CD57+, takes place after BMT engraftment. The occurrence of CMV viremia exerts a substantial effect on this system, causing a steep incline in both curves
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664726&req=5

f4-16-0109: Proposed model for CD8+ T lymphocyte subset reconstitution after BMT and the effect of CMV viremia. A continuous relative decrease in CD28+ cells, along with a continuous relative increase in CD57+, takes place after BMT engraftment. The occurrence of CMV viremia exerts a substantial effect on this system, causing a steep incline in both curves
Mentions: An association between expansion of the CD57+CD8+ T lymphocyte subset and CMV infection in BMT was first suggested by Dolstra et al., who described a higher number of these cells in those patients that developed CMV infection.45 In two patients, CMV-specific cytotoxicity activity was also demonstrated in vitro46. Our findings strongly suggest an association between CMV viremia and the relative expansion of this subset, with an impressive increase of greater than 6% at the time of CMV antigenemia occurrence. The observed temporal association between CMV viremia and the relative increase in the CD57+CD28−CD8+ T lymphocyte subset suggests the presence of an antigen-specific response driven by CMV (Figure 4). However, when patients were divided into allogeneic and autologous BMT groups, we could demonstrate this association only in the allogeneic BMT group.

Bottom Line: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients.Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05).This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Virologia, Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. avamendes@gmail.com

ABSTRACT

Objectives: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients.

Methods: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays.

Results: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01) and an increase in CD57+ lymphocytes (5.60%, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05).

Conclusion: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

Show MeSH
Related in: MedlinePlus