Enhanced cellular immune response and reduced CD8(+) lymphocyte apoptosis in acutely SIV-infected Rhesus macaques after short-term antiretroviral treatment.
Losing the decisive virus-specific functions of both CD4(+) and CD8(+) T lymphocytes in the first weeks after immunodeficiency virus infection ultimately leads to AIDS. The SIV/rhesus monkey model for AIDS was used to demonstrate that a 4-week chemotherapeutic reduction of viral load during acute SIV infection of macaques allowed the development of a competent immune response able to control virus replication after discontinuation of treatment in two of five monkeys. Increasing SIV-specific CD4(+) T-helper-cell proliferation was found in all macaques several weeks after treatment, independent of their viral load. However, only macaques with low viral loads showed persistent T-cell reactivity of lymph node cells. In contrast to animals with higher viral loads, T-helper-cell counts and memory T-helper cells did not decline in the two macaques controlling viral replication. Lymphocyte apoptosis was consistently low in all treated macaques. In contrast, high CD8(+) lymphocyte death but only slightly increased CD4(+) lymphocyte apoptosis were observed during the first weeks after infection in untreated control animals, indicating that early apoptotic death of virus-specific CTL could be an important factor for disease development. Antiretroviral treatment early after infection obviously retained virus-specific and competent T lymphocytes, whereby a virus-specific immune response could develop in two animals able to control the viral replication after cessation of treatment.
Spring
M
M
Department of Virology and Immunology, German Primate Center, Göttingen, Germany. mispri@www.dpz/gwdg.de  
Stahl-Hennig
C
C
Stolte
N
N
Bischofberger
N
N
Heeney
J
J
ten Haaft P
Tenner-Ràcz
K
K
Ràcz
P
P
Lorenzen
D
D
Hunsmann
G
G
Dittmer
U
U
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D008253:Macaca mulatta; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000068698:Tenofovir; D019562:Viral Load
D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine