Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals progressing to AIDS with CMV end-organ disease.
BACKGROUND
Since cytomegalovirus (CMV) infection can cause serious clinical complications in immunocompromised individuals, we assessed cellular immune requirements for protection against CMV end-organ disease (CMV-EOD) in human immunodeficiency virus type 1 (HIV-1) infection.


METHODS
Longitudinal samples from HIV-1-infected patients in the Amsterdam cohort were analyzed. Dynamics of CMV-specific CD8(+) and CD4(+) T cell responses were analyzed by 4-color fluorescence analysis using major histocompatibility class I CMV peptide-tetramers and by intracellular staining for perforin, granzyme B, and interferon (IFN)- gamma after stimulation with CMV-specific stimuli. CMV load was measured in parallel.


RESULTS
In individuals progressing to acquired immunodeficiency syndrome with CMV-EOD, CMV-specific IFN- gamma -producing CD4(+) T cells disappeared during the year before onset of CMV-EOD. This disappearance was accompanied by a sharp increase in CMV load before onset of disease. Despite increasing CMV-specific CD8(+) T cell counts, decreasing CMV-specific IFN- gamma -producing CD8(+) T cell counts were found over time. In contrast, the percentage of CMV-specific perforin- and granzyme B-expressing CD8(+) T cells increased.


CONCLUSIONS
Our data indicate that insufficient help of CD4(+) T cells may cause loss of IFN- gamma -producing CD8(+) T cells and loss of control of CMV dissemination. Increasing CMV-infected cell counts in the face of high CMV-specific perforin- and granzyme B-expressing CD8(+) T cell counts may explain the immune pathological characteristics of CMV disease.
Bronke
Corine
C
Department of Clinical Viro-Immunology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
Palmer
Nanette M
NM
Jansen
Christine A
CA
Westerlaken
Geertje H A
GH
Polstra
Abeltje M
AM
Reiss
Peter
P
Bakker
Margreet
M
Miedema
Frank
F
Tesselaar
Kiki
K
van Baarle
Debbie
D
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology; D017726:Cytomegalovirus Retinitis / Q000150:complications / Q000276:immunology; D018450:Disease Progression; D053804:Granzymes; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009426:Netherlands; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D019562:Viral Load
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases