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. 2005 Mar;7(3):427-36.
doi: 10.1016/j.micinf.2004.11.017. Epub 2005 Feb 24.

Th2 Predominance and CD8+ Memory T Cell Depletion in Patients With Severe Acute Respiratory Syndrome

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Free PMC article

Th2 Predominance and CD8+ Memory T Cell Depletion in Patients With Severe Acute Respiratory Syndrome

Jia-Ling Huang et al. Microbes Infect. .
Free PMC article

Abstract

The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. To define the dynamics of the immune spectrum in SARS, serum levels of cytokines, chemokines, immunoglobulins, complement and specific antibodies against SARS-associated coronavirus (SARS-CoV) were assayed by enzyme-linked immunosorbent assay (ELISA), and phenotypes of peripheral lymphocytes were analyzed by flow cytometry in 95 SARS-infected patients. Results showed that interleukin (IL)-10 and transforming growth factor beta (TGF-beta) were continuously up-regulated during the entirety of SARS. Regulated on activation normally T cell-expressed and secreted (RANTES) levels were decreased, while monocyte chemoattractant protein-1 (MCP-1) was elevated in acute patients. Immunoglobulins and complement were elevated during the first month of SARS. Both serum-positive rates and titers of specific IgM and IgG antibodies responding to SARS-CoV peaked at days 41-60 from the onset of SARS. CD4+ and CD8+ T lymphocytes decreased significantly in acute-phase. CD3+CD8+CD45RO+ T lymphocytes were decreased by 36.78% in the convalescent patients.

Conclusion: SARS-CoV seemed to elicit effective humoral immunity but inhibited cellular immunity, especially CD8+ memory T lymphocytes over time. Prolonged overproduction of IL-10 and TGF-beta may play an important role in the disease.

Figures

Fig. 1
Fig. 1
Profiles of Th1/Th2 cytokines and pro-inflammatory /immunosuppressive cytokines in 95 healthcare workers with SARS, as assayed by ELISA. Serum levels of IFN-γ showed no significant change. IL-2 levels did not change significantly within the first 2 months but decreased during months 3–5. Expression of TNF-β was downregulated within week 1 and again during month 2. IL-10 and TGF-β were continuously overproduced for the entire course of SARS infection. AF, cytokine expression profiles in patients with SARS: A, IL-2; B, IFN-γ; C, IL-10; D, IL-4; E, TNF-β; F, TGF-β. G, RANTES levels in patients at acute and convalescent phases; H, MCP-1 levels in patients at acute and convalescent phases. “w” = week, “ctr” = control, and “m” = month. *: P < 0.05, one-way ANOVA).
Fig. 1
Fig. 1
Profiles of Th1/Th2 cytokines and pro-inflammatory /immunosuppressive cytokines in 95 healthcare workers with SARS, as assayed by ELISA. Serum levels of IFN-γ showed no significant change. IL-2 levels did not change significantly within the first 2 months but decreased during months 3–5. Expression of TNF-β was downregulated within week 1 and again during month 2. IL-10 and TGF-β were continuously overproduced for the entire course of SARS infection. AF, cytokine expression profiles in patients with SARS: A, IL-2; B, IFN-γ; C, IL-10; D, IL-4; E, TNF-β; F, TGF-β. G, RANTES levels in patients at acute and convalescent phases; H, MCP-1 levels in patients at acute and convalescent phases. “w” = week, “ctr” = control, and “m” = month. *: P < 0.05, one-way ANOVA).
Fig. 2
Fig. 2
Percentages of CD3+ of total numbers of PBMCs, percentages of CD4+, CD8+ lymphocytes of total numbers of CD3+ T cells, and CD4/CD8 ratios in acute-phase SARS patients. Percentages of T lymphocytes did not change significantly in acute-phase (P all > 0.30, one-way ANOVA), whereas percentages of CD4+ and CD8+ T lymphocytes decreased significantly (*: vs. the control and convalescent groups, P all < 0.001, one-way ANOVA). Alteration in CD4+ T cell percentage correlated statistically with steroid use (correlation coefficient =–0.372, P < 0.001, Spearman's correlation analysis), whereas CD8+ T lymphocytes did not (correlation coefficient =–0.125, P = 0.401, Spearman's correlation analysis). (A, percentages of T lymphocytes in acute patients; B, percentages of CD4+ T lymphocytes in acute-phase patients; C, percentages of CD8+ T lymphocytes in acute-phase patients. *: P < 0.05, one-way ANOVA). The data were collected under the conditions indicated in Section 2.5, Flow cytometry analisis.
Fig. 2
Fig. 2
Percentages of CD3+ of total numbers of PBMCs, percentages of CD4+, CD8+ lymphocytes of total numbers of CD3+ T cells, and CD4/CD8 ratios in acute-phase SARS patients. Percentages of T lymphocytes did not change significantly in acute-phase (P all > 0.30, one-way ANOVA), whereas percentages of CD4+ and CD8+ T lymphocytes decreased significantly (*: vs. the control and convalescent groups, P all < 0.001, one-way ANOVA). Alteration in CD4+ T cell percentage correlated statistically with steroid use (correlation coefficient =–0.372, P < 0.001, Spearman's correlation analysis), whereas CD8+ T lymphocytes did not (correlation coefficient =–0.125, P = 0.401, Spearman's correlation analysis). (A, percentages of T lymphocytes in acute patients; B, percentages of CD4+ T lymphocytes in acute-phase patients; C, percentages of CD8+ T lymphocytes in acute-phase patients. *: P < 0.05, one-way ANOVA). The data were collected under the conditions indicated in Section 2.5, Flow cytometry analisis.
Fig. 2
Fig. 2
Percentages of CD3+ of total numbers of PBMCs, percentages of CD4+, CD8+ lymphocytes of total numbers of CD3+ T cells, and CD4/CD8 ratios in acute-phase SARS patients. Percentages of T lymphocytes did not change significantly in acute-phase (P all > 0.30, one-way ANOVA), whereas percentages of CD4+ and CD8+ T lymphocytes decreased significantly (*: vs. the control and convalescent groups, P all < 0.001, one-way ANOVA). Alteration in CD4+ T cell percentage correlated statistically with steroid use (correlation coefficient =–0.372, P < 0.001, Spearman's correlation analysis), whereas CD8+ T lymphocytes did not (correlation coefficient =–0.125, P = 0.401, Spearman's correlation analysis). (A, percentages of T lymphocytes in acute patients; B, percentages of CD4+ T lymphocytes in acute-phase patients; C, percentages of CD8+ T lymphocytes in acute-phase patients. *: P < 0.05, one-way ANOVA). The data were collected under the conditions indicated in Section 2.5, Flow cytometry analisis.
Fig. 3
Fig. 3
Spectrum of nonspecific and specific humoral immunity in patients with SARS. General humoral immune parameters (IgA, IgG, IgM, C3, C4) were evaluated automatically from serum samples using Beckman ARRAY 360 System. In specific-antibody ELISA assay, the 96-well polystyrene microplate was pre-coated with lysates of SARS-CoVs and SARS-CoV infected Vero-E6 cells, sera were 10× diluted, and conjugated murine anti-human IgG was used as the second antibody. Levels of IgA, IgG, IgM, C3, and C4, κ light chain were notably elevated during the first month of SARS infection and then decreased to normal levels within 2 months thereafter. Both the seropositive rate and the titer of specific IgM and IgG antibodies responding to SARS-CoV increased, peaking 3 weeks after onset of SARS. (A, IgA, IgG and IgM; B, C3 and C4; C, positive rates of specific IgG and IgM responding to SARS-CoV in patients with SARS; D, optic density of specific IgG and IgM responding to SARS-CoV in patients with SARS. “w” = week, “ctr” = control and “m” = month, “OD” = optical density).
Fig. 3
Fig. 3
Spectrum of nonspecific and specific humoral immunity in patients with SARS. General humoral immune parameters (IgA, IgG, IgM, C3, C4) were evaluated automatically from serum samples using Beckman ARRAY 360 System. In specific-antibody ELISA assay, the 96-well polystyrene microplate was pre-coated with lysates of SARS-CoVs and SARS-CoV infected Vero-E6 cells, sera were 10× diluted, and conjugated murine anti-human IgG was used as the second antibody. Levels of IgA, IgG, IgM, C3, and C4, κ light chain were notably elevated during the first month of SARS infection and then decreased to normal levels within 2 months thereafter. Both the seropositive rate and the titer of specific IgM and IgG antibodies responding to SARS-CoV increased, peaking 3 weeks after onset of SARS. (A, IgA, IgG and IgM; B, C3 and C4; C, positive rates of specific IgG and IgM responding to SARS-CoV in patients with SARS; D, optic density of specific IgG and IgM responding to SARS-CoV in patients with SARS. “w” = week, “ctr” = control and “m” = month, “OD” = optical density).
Fig. 3
Fig. 3
Spectrum of nonspecific and specific humoral immunity in patients with SARS. General humoral immune parameters (IgA, IgG, IgM, C3, C4) were evaluated automatically from serum samples using Beckman ARRAY 360 System. In specific-antibody ELISA assay, the 96-well polystyrene microplate was pre-coated with lysates of SARS-CoVs and SARS-CoV infected Vero-E6 cells, sera were 10× diluted, and conjugated murine anti-human IgG was used as the second antibody. Levels of IgA, IgG, IgM, C3, and C4, κ light chain were notably elevated during the first month of SARS infection and then decreased to normal levels within 2 months thereafter. Both the seropositive rate and the titer of specific IgM and IgG antibodies responding to SARS-CoV increased, peaking 3 weeks after onset of SARS. (A, IgA, IgG and IgM; B, C3 and C4; C, positive rates of specific IgG and IgM responding to SARS-CoV in patients with SARS; D, optic density of specific IgG and IgM responding to SARS-CoV in patients with SARS. “w” = week, “ctr” = control and “m” = month, “OD” = optical density).
Fig. 3
Fig. 3
Spectrum of nonspecific and specific humoral immunity in patients with SARS. General humoral immune parameters (IgA, IgG, IgM, C3, C4) were evaluated automatically from serum samples using Beckman ARRAY 360 System. In specific-antibody ELISA assay, the 96-well polystyrene microplate was pre-coated with lysates of SARS-CoVs and SARS-CoV infected Vero-E6 cells, sera were 10× diluted, and conjugated murine anti-human IgG was used as the second antibody. Levels of IgA, IgG, IgM, C3, and C4, κ light chain were notably elevated during the first month of SARS infection and then decreased to normal levels within 2 months thereafter. Both the seropositive rate and the titer of specific IgM and IgG antibodies responding to SARS-CoV increased, peaking 3 weeks after onset of SARS. (A, IgA, IgG and IgM; B, C3 and C4; C, positive rates of specific IgG and IgM responding to SARS-CoV in patients with SARS; D, optic density of specific IgG and IgM responding to SARS-CoV in patients with SARS. “w” = week, “ctr” = control and “m” = month, “OD” = optical density).

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