Analyzing T-cell responses to cytomegalovirus by cytokine flow cytometry.

T-cell responses to human cytomegalovirus (CMV) are readily detected in chronically infected adults, and are thought to be important for protection from CMV-related pathology. Antigen-specific cytokine flow cytometry (CFC) has been used to establish the range of CMV-specific CD4 and CD8 T-cell frequencies in healthy CMV-seropositive (and seronegative) adults, as well as the dynamics of these cells over time. There are also emerging data regarding the primary CD4 and CD8 T-cell response to CMV in children and adults. Finally, CFC has been used to analyze CMV responses in chronic human immunodeficiency virus infection, as well as during immune reconstitution after bone marrow or stem cell transplantation. These data will be reviewed in terms of what they suggest about the threshold of protective T-cell immunity to CMV, and other factors in addition to T-cell frequencies that could be important in protecting from CMV-associated disease.

[1]  Holden T Maecker,et al.  Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors. , 2002, The Journal of infectious diseases.

[2]  J. Monaco.  Pathways for the processing and presentation of antigens to T cells , 1995, Journal of leukocyte biology.

[3]  R. Ewert,et al.  Measurement of Anti-Human Cytomegalovirus T Cell Reactivity in Transplant Recipients and Its Potential Clinical Use: A Mini-Review , 2000, Intervirology.

[4]  C. Heusser,et al.  Detection of intracellular cytokines by flow cytometry. , 1993, Journal of immunological methods.

[5]  W. Freeman,et al.  Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term survivors of AIDS-related CMV end-organ disease who are receiving potent antiretroviral therapy. , 2001, The Journal of infectious diseases.

[6]  V. Maino,et al.  Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression. , 2000, The Journal of infectious diseases.

[7]  V. Maino,et al.  Direct functional analysis of epitope-specific CD8+ T cells in peripheral blood. , 2001, Viral immunology.

[8]  H. Maecker,et al.  Persistent and Selective Deficiency of CD4+ T Cell Immunity to Cytomegalovirus in Immunocompetent Young Children1 , 2004, The Journal of Immunology.

[9]  Holden T Maecker,et al.  Cytokine flow cytometry. , 2004, Methods in molecular biology.

[10]  V. Maino,et al.  Gamma Interferon Expression in CD8+ T Cells Is a Marker for Circulating Cytotoxic T Lymphocytes That Recognize an HLA A2-Restricted Epitope of Human Cytomegalovirus Phosphoprotein pp65 , 2001, Clinical Diagnostic Laboratory Immunology.

[11]  H. Maecker,et al.  Optimization of whole blood antigen-specific cytokine assays for CD4(+) T cells. , 2000, Cytometry.

[12]  D. Richman,et al.  Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections , 2002, Nature Medicine.

[13]  Decreased HIV-specific CD4 T cell proliferation in long-term HIV-infected individuals on antiretroviral therapy. , 2001, AIDS.

[14]  H. Maecker,et al.  Analysis of the frequencies and of the memory T cell phenotypes of human CD8+ T cells specific for influenza A viruses. , 2003, The Journal of infectious diseases.

[15]  V. Maino,et al.  CD4+CD8dim T lymphocytes exhibit enhanced cytokine expression, proliferation and cytotoxic activity in response to HCMV and HIV‐1 antigens , 2001, European journal of immunology.

[16]  Holden T Maecker,et al.  Performance of plate-based cytokine flow cytometry with automated data analysis , 2003, BMC Immunology.

[17]  J. McCune,et al.  Loss of cytomegalovirus-specific CD4+ T cell responses in human immunodeficiency virus type 1-infected patients with high CD4+ T cell counts and recurrent retinitis. , 2001, The Journal of infectious diseases.

[18]  Daniel C Douek,et al.  References Subscriptions Permissions Email Alerts Direct Ex Vivo Analysis of Human CD4+ Memory T Cell Activation Requirements at the Single Clonotype Level , 2013 .

[19]  J. McCune,et al.  Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1 , 1998, Nature Medicine.

[20]  J. Schneider-Mergener,et al.  T-cell epitope mapping by flow cytometry , 1998, Nature Medicine.

[21]  C. Pitcher,et al.  Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. , 1997, The Journal of clinical investigation.

[22]  R. Koup,et al.  Putative Immunodominant Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype , 2000, Journal of Virology.

[23]  V. Maino,et al.  Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. , 1998, Journal of immunological methods.

[24]  H. Volk,et al.  Analysis of CD8 T cell reactivity to cytomegalovirus using protein‐spanning pools of overlapping pentadecapeptides , 2000, European journal of immunology.

[25]  V. Maino,et al.  Factors Affecting the Efficiency of CD8+ T Cell Cross-Priming with Exogenous Antigens , 2001, The Journal of Immunology.

[26]  D. Nixon,et al.  Direct measurement of CD4+ and CD8+ T-cell responses to CMV in HIV-1-infected subjects. , 2001, Virology.

[27]  D. Speiser,et al.  Ex Vivo IFN-γ Secretion by Circulating CD8 T Lymphocytes: Implications of a Novel Approach for T Cell Monitoring in Infectious and Malignant Diseases1 , 2001, The Journal of Immunology.

[28]  C. Pitcher,et al.  Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus1 , 2001, The Journal of Immunology.

[29]  L. Picker,et al.  Distribution of human CMV‐specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms , 1999, European journal of immunology.

[30]  Douglas D. Richman,et al.  HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function , 2000, The Journal of experimental medicine.

[31]  C. Pitcher,et al.  Use of overlapping peptide mixtures as antigens for cytokine flow cytometry. , 2001, Journal of immunological methods.

[32]  L. Picker,et al.  Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. , 2002, The Journal of infectious diseases.

[33]  S. Rowland-Jones,et al.  Mature CD8(+) T lymphocyte response to viral infection during fetal life. , 2003, The Journal of clinical investigation.

[34]  J. Schneider-Mergener,et al.  Target Structures of the CD8+-T-Cell Response to Human Cytomegalovirus: the 72-Kilodalton Major Immediate-Early Protein Revisited , 1999, Journal of Virology.

[35]  P. Moss,et al.  Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals1 , 2002, The Journal of Immunology.

[36]  V. Maino,et al.  Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis. , 1998, Journal of immunology.

[37]  C. Tournay,et al.  Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. , 2001, Blood.