CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection

• Published in: The Journal of immunology (1950) Vol. 173; no. 4; pp. 2410 - 2418
• Main Authors: Doisne, Jean-Marc, Urrutia, Alejandra, Lacabaratz-Porret, Christine, Goujard, Cecile, Meyer, Laurence, Chaix, Marie-Laure, Sinet, Martine, Venet, Alain
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2004; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
• Subjects: ADP-ribosyl Cyclase - biosynthesis; ADP-ribosyl Cyclase - immunology; ADP-ribosyl Cyclase 1; Adult; Animals; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Differentiation - biosynthesis; Antigens, Differentiation - immunology; Antiretroviral Therapy, Highly Active; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus - immunology; Female; Herpesvirus 4, Human - immunology; HIV - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - immunology; Humans; Ki-67 Antigen - biosynthesis; Ki-67 Antigen - immunology; Life Sciences; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; Membrane Glycoproteins; Orthomyxoviridae - immunology; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - immunology; Viral Load
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.4.2410

Primary viral infections, including primary HIV infection, trigger intense activation of the immune system, with marked expansion of CD38(+)CD8(+) T cells. Whether this expansion involves only viral-specific cells or includes a degree of bystander activation remains a matter of debate. We therefore examined the activation status of EBV-, CMV-, and influenza virus (FLU)-specific CD8(+) T cells during primary HIV infection, in comparison to HIV-specific CD8(+) T cells. The activation markers CD38 and HLA-DR were strongly expressed on HIV-specific CD8(+) T cells. Surprisingly, CD38 expression was also up-regulated on CD8(+) T cells specific for other viruses, albeit to a lesser extent. Activation marker expression returned to normal or near-normal values after 1 year of highly active antiretroviral therapy. HIV viral load correlated with CD38 expression on HIV-specific CD8(+) T cells but also on EBV-, CMV-, and FLU-specific CD8(+) T cells. In primary HIV infection, EBV-specific CD8(+) T cells also showed increased Ki67 expression and decreased Bcl-2 expression, compared with values observed in HIV-seronegative control subjects. These results show that bystander activation occurs during primary HIV infection, even though HIV-specific CD8(+) T cells express the highest level of activation. The role of this bystander activation in lymphocyte homeostasis and HIV pathogenesis remains to be determined.