Comparison of activation marker and TCR Vβ gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients

Publisher Website
Google Scholar
Abstract
SUMMARY: Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) Vβ gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-Vβ MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the Vβ repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of Vβ families expressed by CD4+ or CDS+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more Vβ families exhibited different distributions and these differences recurred among certain Vβ segments, such as Vβ5.3 and Vβ21 in the CD4+ T cell population and Vβ5.2/5.3, Vβ12 and Vβ12 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.