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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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Cytokine CD4+ (A) and CD8+ (B) production, CD8+ lysis molecules expression (C) and lymphocyte proliferation (D) in ASCT recipients (ASCT), in HIV-infected patients (HIV) and in healthy controls (HC).ASCT recipients displayed significantly higher levels of TNF-α and IFN-γ producing CD8+ T cells under basal conditions and of TNF-α+ CD8+ T cells under Staphylococcal β enterotoxin (SEB) stimulation compared to HIV-infected patients. CD4+ IL-2 and IFN-γ production after SEB stimulation was globally depressed in both group of patients compared to healthy controls. The fraction of CD8+ T cells expressing granzyme B was higher in ASCT recipients than in HIV-infected patients. Antigen-induced proliferative responses showed comparable stimulation index values in both patients population and for polyclonal activation (PHA) as well as antigen stimulation (Flu, Candida), with significant difference with healthy controls regarding Flu stimulation. * = p<0.05 in the comparison between groups.
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pone-0003616-g004: Cytokine CD4+ (A) and CD8+ (B) production, CD8+ lysis molecules expression (C) and lymphocyte proliferation (D) in ASCT recipients (ASCT), in HIV-infected patients (HIV) and in healthy controls (HC).ASCT recipients displayed significantly higher levels of TNF-α and IFN-γ producing CD8+ T cells under basal conditions and of TNF-α+ CD8+ T cells under Staphylococcal β enterotoxin (SEB) stimulation compared to HIV-infected patients. CD4+ IL-2 and IFN-γ production after SEB stimulation was globally depressed in both group of patients compared to healthy controls. The fraction of CD8+ T cells expressing granzyme B was higher in ASCT recipients than in HIV-infected patients. Antigen-induced proliferative responses showed comparable stimulation index values in both patients population and for polyclonal activation (PHA) as well as antigen stimulation (Flu, Candida), with significant difference with healthy controls regarding Flu stimulation. * = p<0.05 in the comparison between groups.

Mentions: To determine whether the relevant phenotypic characteristics are associated with selective defects in cytokine production in ASCT recipients compared to HIV-infected subjects, we tested the capacity of CD4+ T cells to produce IL-2 and IFN-γ in response to superantigen stimulation (fig. 4A). Profound impairment in IL-2 and IFN-γ production after SEB stimulation was found in both group of patients with respect to age-matched healthy controls (IL-2+/CD4+ ASCT 1.18%, HIV 0.4%, HC 5.28%, p<0.05 for HC versus ASCT and HIV; IFN-γ+/CD4+ ASCT 0.96%, HIV 1.2%, HC 2.59%, p = ns).These observations suggest that CD4+ T cells activated via T-cell receptor stimulation are dramatically weakened in their capacity to produce IL-2 and IFN-γ, both in ASCT recipients and in HIV disease.


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)

Cytokine CD4+ (A) and CD8+ (B) production, CD8+ lysis molecules expression (C) and lymphocyte proliferation (D) in ASCT recipients (ASCT), in HIV-infected patients (HIV) and in healthy controls (HC).ASCT recipients displayed significantly higher levels of TNF-α and IFN-γ producing CD8+ T cells under basal conditions and of TNF-α+ CD8+ T cells under Staphylococcal β enterotoxin (SEB) stimulation compared to HIV-infected patients. CD4+ IL-2 and IFN-γ production after SEB stimulation was globally depressed in both group of patients compared to healthy controls. The fraction of CD8+ T cells expressing granzyme B was higher in ASCT recipients than in HIV-infected patients. Antigen-induced proliferative responses showed comparable stimulation index values in both patients population and for polyclonal activation (PHA) as well as antigen stimulation (Flu, Candida), with significant difference with healthy controls regarding Flu stimulation. * = p<0.05 in the comparison between groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003616-g004: Cytokine CD4+ (A) and CD8+ (B) production, CD8+ lysis molecules expression (C) and lymphocyte proliferation (D) in ASCT recipients (ASCT), in HIV-infected patients (HIV) and in healthy controls (HC).ASCT recipients displayed significantly higher levels of TNF-α and IFN-γ producing CD8+ T cells under basal conditions and of TNF-α+ CD8+ T cells under Staphylococcal β enterotoxin (SEB) stimulation compared to HIV-infected patients. CD4+ IL-2 and IFN-γ production after SEB stimulation was globally depressed in both group of patients compared to healthy controls. The fraction of CD8+ T cells expressing granzyme B was higher in ASCT recipients than in HIV-infected patients. Antigen-induced proliferative responses showed comparable stimulation index values in both patients population and for polyclonal activation (PHA) as well as antigen stimulation (Flu, Candida), with significant difference with healthy controls regarding Flu stimulation. * = p<0.05 in the comparison between groups.
Mentions: To determine whether the relevant phenotypic characteristics are associated with selective defects in cytokine production in ASCT recipients compared to HIV-infected subjects, we tested the capacity of CD4+ T cells to produce IL-2 and IFN-γ in response to superantigen stimulation (fig. 4A). Profound impairment in IL-2 and IFN-γ production after SEB stimulation was found in both group of patients with respect to age-matched healthy controls (IL-2+/CD4+ ASCT 1.18%, HIV 0.4%, HC 5.28%, p<0.05 for HC versus ASCT and HIV; IFN-γ+/CD4+ ASCT 0.96%, HIV 1.2%, HC 2.59%, p = ns).These observations suggest that CD4+ T cells activated via T-cell receptor stimulation are dramatically weakened in their capacity to produce IL-2 and IFN-γ, both in ASCT recipients and in HIV disease.

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