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Fully immunocompetent CD8+ T lymphocytes are present in autologous haematopoietic stem cell transplantation recipients despite an ineffectual T-helper response.

Bandera A, Trabattoni D, Pacei M, Fasano F, Suardi E, Cesari M, Marchetti G, Pogliani EM, Franzetti F, Clerici M, Gori A - PLoS ONE (2008)

Bottom Line: Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression.The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Internal Medicine, "San Gerardo" Hospital, University of Milan-Bicocca, Monza, Italy. a.bandera@hsgerardo.org

ABSTRACT

Background: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients.

Methodology/principal findings: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.

Conclusion/significance: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.

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Related in: MedlinePlus

Ratios of CD4+ and CD8+ lymphocytes subsets across ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls.ASCT recipients and HIV-infected patients displayed similar ratios between CD4+ subpopulations, CD45RA−CCR7+(CM)/CD45RA−CCR7− (EM). CD45RA−CCR7−CD8+(EM)/CD45RA+CCR7−CD8+(TD) ratio was significantly lower in ASCT recipients compared to HIV+ patients, with no differences in CD45RA−CCR7+ CD8+ (CM)/CD45RA−CCR7− CD8+ (EM) and CD45RA−CCR7+ CD8+ (CM)/ CD45RA+CCR7−CD8+ (TD) ratios among the two group of patients.
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pone-0003616-g003: Ratios of CD4+ and CD8+ lymphocytes subsets across ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls.ASCT recipients and HIV-infected patients displayed similar ratios between CD4+ subpopulations, CD45RA−CCR7+(CM)/CD45RA−CCR7− (EM). CD45RA−CCR7−CD8+(EM)/CD45RA+CCR7−CD8+(TD) ratio was significantly lower in ASCT recipients compared to HIV+ patients, with no differences in CD45RA−CCR7+ CD8+ (CM)/CD45RA−CCR7− CD8+ (EM) and CD45RA−CCR7+ CD8+ (CM)/ CD45RA+CCR7−CD8+ (TD) ratios among the two group of patients.

Mentions: In stark contrast, the CD45RA−CCR7−CD8+ and CD45RA+CCR7−CD8+ ratio was significantly higher in HIV+ patients compared to ASCT recipients, who displayed values similar to healthy controls (ASCT 1.83, HIV 5.77, HC 0.97, p<0.05 for HIV versus ASCT and HC). This observation underlines the over-representation of pre-terminally differentiated CD8+ T cells and the simultaneously lower levels of terminally differentiated CD8+ T cells in HIV population (Fig. 3).


Fully immunocompetent CD8+ T lymphocytes are present in autologous haematopoietic stem cell transplantation recipients despite an ineffectual T-helper response.

Bandera A, Trabattoni D, Pacei M, Fasano F, Suardi E, Cesari M, Marchetti G, Pogliani EM, Franzetti F, Clerici M, Gori A - PLoS ONE (2008)

Ratios of CD4+ and CD8+ lymphocytes subsets across ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls.ASCT recipients and HIV-infected patients displayed similar ratios between CD4+ subpopulations, CD45RA−CCR7+(CM)/CD45RA−CCR7− (EM). CD45RA−CCR7−CD8+(EM)/CD45RA+CCR7−CD8+(TD) ratio was significantly lower in ASCT recipients compared to HIV+ patients, with no differences in CD45RA−CCR7+ CD8+ (CM)/CD45RA−CCR7− CD8+ (EM) and CD45RA−CCR7+ CD8+ (CM)/ CD45RA+CCR7−CD8+ (TD) ratios among the two group of patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2570790&req=5

pone-0003616-g003: Ratios of CD4+ and CD8+ lymphocytes subsets across ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls.ASCT recipients and HIV-infected patients displayed similar ratios between CD4+ subpopulations, CD45RA−CCR7+(CM)/CD45RA−CCR7− (EM). CD45RA−CCR7−CD8+(EM)/CD45RA+CCR7−CD8+(TD) ratio was significantly lower in ASCT recipients compared to HIV+ patients, with no differences in CD45RA−CCR7+ CD8+ (CM)/CD45RA−CCR7− CD8+ (EM) and CD45RA−CCR7+ CD8+ (CM)/ CD45RA+CCR7−CD8+ (TD) ratios among the two group of patients.
Mentions: In stark contrast, the CD45RA−CCR7−CD8+ and CD45RA+CCR7−CD8+ ratio was significantly higher in HIV+ patients compared to ASCT recipients, who displayed values similar to healthy controls (ASCT 1.83, HIV 5.77, HC 0.97, p<0.05 for HIV versus ASCT and HC). This observation underlines the over-representation of pre-terminally differentiated CD8+ T cells and the simultaneously lower levels of terminally differentiated CD8+ T cells in HIV population (Fig. 3).

Bottom Line: Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression.The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Internal Medicine, "San Gerardo" Hospital, University of Milan-Bicocca, Monza, Italy. a.bandera@hsgerardo.org

ABSTRACT

Background: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients.

Methodology/principal findings: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.

Conclusion/significance: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.

Show MeSH
Related in: MedlinePlus