AEGiS-11IAC: Kinetics of EBV-specific cytotoxic T cell response in patients with AIDS-related non-Hodgkin's lymphoma.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Kinetics of EBV-specific cytotoxic T cell response in patients with AIDS-related non-Hodgkin's lymphoma.

Int Conf AIDS 1996 Jul 7-12; 11:15 (abstract no. We.A.403)
Miedema F, Kersten MJ, Klein MR, Holwerda AM, Van Oers MH; Dept. of Clin. Viro-Immunology, Central Lab. Netherlands Red Cross Blood Transfusion Service and Lab. for Exp. and Clin. Immunol. of the University of Amsterdam, Amsterdam, The Netherlands. Fax: +31 20 512 3310.

OBJECTIVE: The vast majority of AIDS-NHL are diffuse large-cell and immunoblastic lymphomas, thought to arise because of uncontrolled EBV-driven proliferation of B cells. EBV-specific CD8+ MHC class I-restricted cytotoxic T lymphocytes (CTL) are known to play a key role in EBV-specific immunity in healthy individuals. This study was aimed at two questions: 1. What is the temporal relationship between EBV-specific CTL-precursors (CTLp) and EBV load (latently EBV-infected B cells) in the course of HIV infection, and how does this relate to changes in T cell reactivity and HIV-specific CTLp? 2. Are there differences in frequency and/or kinetics of EBV-CTLp and EBV load between HIV-infected patients who develop NHL and those who do not?

METHODS: A sensitive limiting dilution assay was developed to measure the frequency of EBV-CTLp by using targets infected with recombinant vaccinia viruses expressing the immunodominant EBV latent antigens. EBV-load was quantitated with an assay for spontaneous B cell transformation. Patient material consisted of cryopreserved PBMC samples from the Amsterdam Cohort Study on AIDS, obtained at regular intervals over a period of 4-8 years preceding the NHL or other AIDS-defining diagnoses. Results. In 2 long-term asymptomatic HIV-infected individuals (normal CD4 counts and T cell reactivity 10 years after seroconversion) both HIV-CTLp and EBV-CTLp remained stable with low HIV and EBV viral load. In 5 progressors to AIDS (PCP) HIV load increased despite strong and mounting HIV-CTLp early in infection. During clinical progression to AIDS HIV-CTL were lost. EBV-CTLp remained stable in 2 of these progressors and decreased in parallel with deteriorating T cell function in the other 3. In all 5 progressors EBV load remained low. In contrast, in 4/5 patients with AIDS-NHL EBV load was considerably increased already several years preceding the NHL. In 2 of these patients EBV-CTLp were initially high and increasing; prior to the emergence of the NHL EBV-CTL were low to absent in all patients. Conclusion. These data suggest that although CTL responses are mounted to HIV- and EBV-infected cells and may have contributed to initial control of virus replication, they eventually failed to prevent disease progression.

Keywords: AEGIS, Lymphoma, AIDS-Related, T-Lymphocytes, Cytotoxic, Herpesvirus 4, Human, HIV Infections, Acquired Immunodeficiency Syndrome, Viral Load, CD4 Lymphocyte Count, HIV, Disease Progression, Antigens, CD8, HIV Long-Term Survivors, HIV Antigens, Virus Replication, Kinetics, Cohort Studies, Human, virology, ICA11

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