AEGiS-15IAC: High CD4 cell counts correlate with enhanced maturation of virus-specific CD8+T cells.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

High CD4 cell counts correlate with enhanced maturation of virus-specific CD8+T cells.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1003)

L Caccavelli¹, S Imbart¹, Y Levy², L Weiss¹
¹Hôpital Européen Georges Pompidou and Université Paris V, Paris, France; ²Hôpital Henri Mondor, Créteil, France

BACKGROUND: It has been demonstrated that HIV-specific CD8+ T cells were predominantly composed of pre-terminally differentiated CD45RA-CCR7- cells whereas CMV-specific CD8+ T cells consisted mainly of terminally differentiated cells (CD45RA+CCR7-) shown to be effector cells expressing perforine and granzyme. The aim of the study was to investigate if there is a relationship between CD4 cell counts in untreated and ART-treated patients and the stage of maturation of CMV- and HIV-specific CD8+ T cells. Patients and

METHODS: 38 HLA-A2 patients were included in the study. 74% exhibited detectable plasma HIV-RNA. The median CD4 cell count was 592/mm³. CD8+ T cells in whole blood were stained with anti-CCR7-FITC mAb, anti-CD45RA-PyC5 mAb and either the A2 SLYNTVATL gag tetramer-PE or the A2 NLVPMVATV-pp65 tetramer-PE.

RESULTS: CMV and HIV-tetramer + CD8 T cells were detected in 82% and 42% of patients, respectively. Among CD8 T cells, the mean percentage (ranges) of tetramer + cells were 1.78 (0.04-7.46) and 0.67 (0.05-2.32) for CMV and HIV, respectively. In agreement with previous reports, CMV-specific CD8+ T cells were mainly CD45RA+CCR7- thus terminally differentiated (61%, n=31) whereas HIV-specific CD8+ T cells were mainly pre-terminally differentiated CD45RA-CCR7- (80%, n=16). CMV-specific CD8+ T cells expressed more frequently a CD45RA+CCR7- phenotype in patients with CD4 T cells >500 compared to those with CD4 T cells< 500 (67% vs 49%, p= 0.021). There is a trend towards a higher frequency of HIV-specific CD8+ T cells expressing a CD45RA+CCR7- phenotype in patients with CD4 >500 (22% vs 15% in patients with CD4< 500). In 2 patients with high CD4+ T cells under IL-2 therapy, the majority (91.5±1.1%) of CMV-specific T cells exhibited a terminally differentiated phenotype.

CONCLUSIONS: Our results provide evidence for a role of CD4 T cell help in improving the block of maturation of virus-specific CD8 T cells which impairs cytolytic activity and viral control.

Keywords: AEGIS, Antigens, CD8, Antigens, CD45, CD4-Positive T-Lymphocytes, HIV, Virus Diseases, Antigens, CD4, HIV Infections, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Humans, immunology

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MoOrA1003