Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1364-1371
Proliferation and Apoptosis-Related Gene Expression in Experimental
Acquired Immunodeficiency Syndrome-Related Simian Lymphoma
Esmeralda Castaños-Vélez,
Thomas Heiden,
Marianne Ekman,
Joseph Lawrence,
Gunnel Biberfeld, and
Peter Biberfeld
From the Immunopathology Laboratory, Karolinska Institute/Hospital,
Stockholm, Sweden; the Swedish Institute for Infectious Diseases
Control and Karolinska Institute, Stockholm, Sweden; and
the Department of Medical Radiobiology, Karolinska
Institute, Stockholm, Sweden.
Lymphomas in 10 cynomolgus monkeys infected with a simian
immunodeficiency virus (SIVsm) were studied with regard to
proliferative activity and apoptosis-related gene expression. All were
diffuse large-cell lymphomas, showed mono or oligoclonality and a 9/10 diploid cellular DNA content. Expression of a simian homologue to
Epstein-Barr virus (HVMF-1) was shown in nine cases. The lymphomas showed moderate to high proliferative activity by Ki67 immunostaining and DNA flow cytometry, and a low number of apoptotic cells detected by
TdT-mediated dUTP nick-end labeling (TUNEL).
Immunohistochemistry showed abundant tumor infiltrating
TIA-1+ cytotoxic lymphocytes (CTL) and macrophages.
Bcl-2, Mcl-1, and also Bax and Bak, but not p53 were demonstrable in
the tumor cells by immunostaining. Our findings suggest a causal
relationship between HVMF-1 infection and a low apoptotic index of the
lymphomas due to the expression of Bcl-2. The apparent inefficient
function of tumor-infiltrating CTL could be due to inactivation of CTL and/or resistance of the lymphoma cells to CTL effects. The
tumors showed immunoreactivity for CD18, CD29, and CD49d, but not for CD11a, mimicking the phenotype of human Epstein-Barr virus
(EBV)-related lymphomas. In summary, our observations indicate a high
similarity between this simian model of acquired immunodeficiency
syndrome (AIDS)-related lymphomas (ARL) and human ARL and other
immunosuppression-related lymphomas.
