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CD8⁺ T Cell Dynamics during Primary Simian Immunodeficiency Virus Infection in Macaques: Relationship of Effector Cell Differentiation with the Extent of Viral Replication¹

Valérie Monceaux^*, Laurence Viollet^2,*, Frédéric Petit^2,*, Raphaël Ho Tsong Fang^*, Marie-Christine Cumont^*, John Zaunders, Bruno Hurtrel^* and Jérôme Estaquier^3,*

^* Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France; and Centre for Immunology, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia

Immunological and virological events that occur during the earliest stages of HIV-1 infection are now considered to have a major impact on subsequent disease progression. We observed changes in the frequencies of CD8^bright T cells expressing different chemokine receptors in the peripheral blood and lymph nodes of rhesus macaques during the acute phase of the pathogenic SIVmac251 infection; the frequency of CD8^bright T cells expressing CXCR4 decreased, while the frequency of those expressing CCR5 increased. These reciprocal changes in chemokine receptor expression were associated with changes in the proportion of cycling (Ki67⁺) CD8^bright T cells, and with the pattern of CD8^bright T cell differentiation as defined by expression of CCR7 and CD45RA. In contrast, during the primary phase of the attenuated SIVmac251nef infection, no major change was observed. Whereas during the acute phase of the infection with pathogenic SIV (2 wk postinfection) no correlate of disease protection was identified, once the viral load set points were established (2 mo postinfection), we found that the levels of cycling and of CCR5- and CXCR4-positive CD8^bright T cells were correlated with the extent of viral replication and therefore with SIV-infection outcome. Our data reveal that, during primary SIV infection, despite intense CD8 T cell activation and an increase in CCR5 expression, which are considered as essential for optimal effector function of CD8⁺ T cells, these changes are associated with a poor prognosis for disease progression to AIDS.

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