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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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CD8+ T cell maturation patterns lymphocytes in ASCT recipients (ASCT), in HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD8+ T cells (CD45RA+CCR7+) (A), central memory (CD45RA−CCR7+) (B), effector memory (CD45RA−CCR7−) (C) and effector cells (CD45RA+CCR7−) (D) were compared in the groups. Higher levels of naïve CD8+ T-cells were observed in ASCT recipients compared to HIV+ patients. Whereas in HIV positive patients effector memory CD8+ T cells were the predominant memory phenotype, in ASCT recipients significantly higher levels of CD45RA+CCR7− effector CD8+ cells were evidenced. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.
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pone-0003616-g002: CD8+ T cell maturation patterns lymphocytes in ASCT recipients (ASCT), in HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD8+ T cells (CD45RA+CCR7+) (A), central memory (CD45RA−CCR7+) (B), effector memory (CD45RA−CCR7−) (C) and effector cells (CD45RA+CCR7−) (D) were compared in the groups. Higher levels of naïve CD8+ T-cells were observed in ASCT recipients compared to HIV+ patients. Whereas in HIV positive patients effector memory CD8+ T cells were the predominant memory phenotype, in ASCT recipients significantly higher levels of CD45RA+CCR7− effector CD8+ cells were evidenced. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.

Mentions: A wholly different scenario was evidenced when CD8+ T cell maturation patterns were analyzed in ASCT recipients and in HIV-infected subjects (Fig. 2). Indeed, while ASCT recipients displayed levels of CD45RA+CCR7+ CD8+ T-cells comparable with healthy controls (ASCT 28.83%; HIV 26.9%; p>0.05), significant reduced levels of naïve CD8 T cells were seen in HIV+ patients (6.07%, p<0.05 for HIV versus HC). Moreover, while CD45RA−CCR7− CD8+ T cells predominated in HIV positive patients, levels of these pre-terminally differentiated cells were significantly lower in ASCT recipients and in healthy controls (ASCT 36.4%, HIV 62.6%, HC 32.3%, p<0.05 for HIV versus ASCT and HC). Higher levels of CD45RA+CCR7− effector CD8+ cells were present in ASCT recipients than in HIV-infected subjects (ASCT 21.07%, HIV 12.55%, p = 0.05), who displayed significantly lower levels of terminal differentiated CD8+ T cells compared to healthy controls (HC 33.2%, p<0.05 for HIV versus HC). These data demonstrate that, unlike the chronic viral model, in ASCT recipients the rapidly replicating CD8+ T cell compartment follow a phenotypic distribution biased toward a terminally differentiated effector cell phenotype.


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)

CD8+ T cell maturation patterns lymphocytes in ASCT recipients (ASCT), in HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD8+ T cells (CD45RA+CCR7+) (A), central memory (CD45RA−CCR7+) (B), effector memory (CD45RA−CCR7−) (C) and effector cells (CD45RA+CCR7−) (D) were compared in the groups. Higher levels of naïve CD8+ T-cells were observed in ASCT recipients compared to HIV+ patients. Whereas in HIV positive patients effector memory CD8+ T cells were the predominant memory phenotype, in ASCT recipients significantly higher levels of CD45RA+CCR7− effector CD8+ cells were evidenced. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003616-g002: CD8+ T cell maturation patterns lymphocytes in ASCT recipients (ASCT), in HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD8+ T cells (CD45RA+CCR7+) (A), central memory (CD45RA−CCR7+) (B), effector memory (CD45RA−CCR7−) (C) and effector cells (CD45RA+CCR7−) (D) were compared in the groups. Higher levels of naïve CD8+ T-cells were observed in ASCT recipients compared to HIV+ patients. Whereas in HIV positive patients effector memory CD8+ T cells were the predominant memory phenotype, in ASCT recipients significantly higher levels of CD45RA+CCR7− effector CD8+ cells were evidenced. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.
Mentions: A wholly different scenario was evidenced when CD8+ T cell maturation patterns were analyzed in ASCT recipients and in HIV-infected subjects (Fig. 2). Indeed, while ASCT recipients displayed levels of CD45RA+CCR7+ CD8+ T-cells comparable with healthy controls (ASCT 28.83%; HIV 26.9%; p>0.05), significant reduced levels of naïve CD8 T cells were seen in HIV+ patients (6.07%, p<0.05 for HIV versus HC). Moreover, while CD45RA−CCR7− CD8+ T cells predominated in HIV positive patients, levels of these pre-terminally differentiated cells were significantly lower in ASCT recipients and in healthy controls (ASCT 36.4%, HIV 62.6%, HC 32.3%, p<0.05 for HIV versus ASCT and HC). Higher levels of CD45RA+CCR7− effector CD8+ cells were present in ASCT recipients than in HIV-infected subjects (ASCT 21.07%, HIV 12.55%, p = 0.05), who displayed significantly lower levels of terminal differentiated CD8+ T cells compared to healthy controls (HC 33.2%, p<0.05 for HIV versus HC). These data demonstrate that, unlike the chronic viral model, in ASCT recipients the rapidly replicating CD8+ T cell compartment follow a phenotypic distribution biased toward a terminally differentiated effector cell phenotype.

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