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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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Phenotypical maturation pattern of CD4+ lymphocytes in ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD4+ 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. ASCT recipients and HIV-infected patients displayed low percentages of naïve and central memory CD4+ T cells. A relative expansion of effector memory cells was observed in both population. 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-g001: Phenotypical maturation pattern of CD4+ lymphocytes in ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD4+ 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. ASCT recipients and HIV-infected patients displayed low percentages of naïve and central memory CD4+ T cells. A relative expansion of effector memory cells was observed in both population. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.

Mentions: We investigated phenotypical maturation pattern of lymphocytes in ASCT recipients and in HIV patients, analyzing cells based on the expression of CD45 isoforms and chemokine receptor CCR7. Despite contrasting clinical risk, ASCT recipients displayed a skewed CD4+ phenotype distribution very similar to what observed in HIV-infected subjects (Fig. 1). Indeed, the fraction of naïve CD4+ T cells (CD45RA+CCR7+) was significantly lower in both population compared to healthy controls (ASCT, 5.49%; HIV, 8.13%;HC, 35,9%; p<0.05 for HC versus ASCT and HIV; p>0.05 for ASCT versus HIV). Moreover, an expansion of effector memory CD45RA−CCR7− cells was seen both in ASCT and in HIV-infected patients with respect to age-matched healthy subjects (ASCT 62.6%; HIV 62.3%; HC 27.8%; p<0.05 for HC versus ASCT and HIV; p>0.05 for ASCT versus HIV), while ASCT recipients displayed the highest levels of effector CD45RA+CCR7− cells (ASCT 11.2%, HIV 2.18%, HC 1.89, p< 0.05 for ASCT versus HC, p>0.05 for ASCT versus HIV). Central memory cells (CD45RA−CCR7+), which have been recognized as the predominant CD4+ subpopulation in healthy controls together with naïve CD4+ T cells, were evidenced at lower frequency in ASCT recipients (8.48%) and HIV-infected subjects (17.9%), with statistical significance in the comparison between ASCT patients and healthy subjects (ASCT 8.48%, HIV 17.9%, HC 33.1%, p<0.05 for ASCT versus HC, p>0.05 for HIV versus ASCT and HC). Similarly to what observed in HIV-infected patients, ASCT recipients present a phenotypic CD4+ pattern characterized by a relative expansion of effector memory cells and a loss of central memory cells, which has been hypothesized disadvantageous in chronic infections.


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)

Phenotypical maturation pattern of CD4+ lymphocytes in ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD4+ 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. ASCT recipients and HIV-infected patients displayed low percentages of naïve and central memory CD4+ T cells. A relative expansion of effector memory cells was observed in both population. 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-g001: Phenotypical maturation pattern of CD4+ lymphocytes in ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls (HC).The percentage of naïve CD4+ 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. ASCT recipients and HIV-infected patients displayed low percentages of naïve and central memory CD4+ T cells. A relative expansion of effector memory cells was observed in both population. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range.
Mentions: We investigated phenotypical maturation pattern of lymphocytes in ASCT recipients and in HIV patients, analyzing cells based on the expression of CD45 isoforms and chemokine receptor CCR7. Despite contrasting clinical risk, ASCT recipients displayed a skewed CD4+ phenotype distribution very similar to what observed in HIV-infected subjects (Fig. 1). Indeed, the fraction of naïve CD4+ T cells (CD45RA+CCR7+) was significantly lower in both population compared to healthy controls (ASCT, 5.49%; HIV, 8.13%;HC, 35,9%; p<0.05 for HC versus ASCT and HIV; p>0.05 for ASCT versus HIV). Moreover, an expansion of effector memory CD45RA−CCR7− cells was seen both in ASCT and in HIV-infected patients with respect to age-matched healthy subjects (ASCT 62.6%; HIV 62.3%; HC 27.8%; p<0.05 for HC versus ASCT and HIV; p>0.05 for ASCT versus HIV), while ASCT recipients displayed the highest levels of effector CD45RA+CCR7− cells (ASCT 11.2%, HIV 2.18%, HC 1.89, p< 0.05 for ASCT versus HC, p>0.05 for ASCT versus HIV). Central memory cells (CD45RA−CCR7+), which have been recognized as the predominant CD4+ subpopulation in healthy controls together with naïve CD4+ T cells, were evidenced at lower frequency in ASCT recipients (8.48%) and HIV-infected subjects (17.9%), with statistical significance in the comparison between ASCT patients and healthy subjects (ASCT 8.48%, HIV 17.9%, HC 33.1%, p<0.05 for ASCT versus HC, p>0.05 for HIV versus ASCT and HC). Similarly to what observed in HIV-infected patients, ASCT recipients present a phenotypic CD4+ pattern characterized by a relative expansion of effector memory cells and a loss of central memory cells, which has been hypothesized disadvantageous in chronic infections.

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