Shift of CMV-specific CD4+ T-cells to the highly differentiated CD45RO-CD27- phenotype parallels loss of proliferative capacity and precedes progression to HIV-related CMV end-organ disease.
To identify factors related to progression to CMV end-organ disease, cytokine production, proliferative capacity and phenotype of CMV-specific CD4(+) T-cells were analysed longitudinally. Numbers of IFNgamma(+)CD4(+) and IFNgamma(+)IL-2(+)CD4(+) T-cells tended to decrease in individuals progressing to AIDS with CMV end-organ disease (AIDS-CMV), whereas they remained detectable in long-term asymptomatics (LTAs) and progressors to AIDS with opportunistic infections (AIDS-OI). In parallel, CMV-specific proliferative capacity was lost in AIDS-CMV. Initially, the majority of the CMV-specific IFNgamma(+)CD4(+) T-cells were of the CD45RO(+)CD27(-) subset, but during progression to AIDS-CMV a shift in phenotype to the CD45RO(-)CD27(-) subset was observed. Our data indicate that a decrease in CMV-specific cytokine production and proliferative capacity precedes progression to AIDS-CMV. Accumulation of CD4(+) T-cells with a CD45RO(-)CD27(-) phenotype suggests that persistent antigen exposure drives differentiation of CMV-specific CD4(+) T-cells towards a poorly proliferating, and highly differentiated "effector" subset, which eventually fails to produce IFNgamma in patients developing AIDS-CMV.
Bronke
Corine
C
Department of Clinical Viro-Immunology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Jansen
Christine A
CA
Westerlaken
Geertje H A
GH
De Cuyper
Iris M
IM
Miedema
Frank
F
Tesselaar
Kiki
K
van Baarle
Debbie
D
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D018450:Disease Progression; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens