Jin Fan[1,2], Hua Liang[2], Tao Shen[1], Shuo Wang[2], Xiaolin Ji[2], Cassian Yee[3], Fengmin Lu[1], Yiming Shao[1,2]

Affiliates

[1]Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Haidian District, Beijing 100191, China; [2]State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China; [3]Department of Melanoma Medical Oncology, Department of Immunology, UT MD Anderson Cancer Center, Houston, TX 77054, United States

Abstract

Background: Though the contribution of Gag-specific CD8 T cell responses to early viral control is well established, little is known about the role of Env-specific CD8 T cell responses in controlling viral replication during acute infection. In a macaque SHIV model, some macaques who were able to control SHIV replication after ART interruption showed expansion of Env-specific CD8 T cell responses during acute infection, compared to macaques who progressed to viral rebound. To better understand the function of early Env-specific CD8 T cells, we isolated, expanded and examined their ability to act as effectors in vitro.
Methods and Results: We generated early Env-specific CD8 T cell from the peripheral blood of SHIV controller macaques. Followed by Env peptide stimulation, CD3+CD8+CD4-CD137+ cells of each macaques were sorted and expanded. Specific antigen recognition and antiviral activity were confirmed for each T cell clones generated in this manner. We observed that Env-specific CD8 T cell clones have the capacity to directly recognize and kill SHIV-infected CD4 T cells, but failed to reduce viral replication in SHIV-infected macrophages.
Conclusions: Our data suggest that early Env-specific CD8 T cell responses during acute SHIV infection contribute substantially to the control of viral replication. The T-cell clones composing of Env-specific effector cells demonstrates in vitro phenotypic and functional characteristics with the potentials to provide long-lasting clinical benefit of in vivo HIV study.