Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections

Abstract

The objective of this study was to functionally assess gamma/delta (␥␦) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. ␥␦ T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4 ؉ T cells/l blood) or CD4-low (<200 CD4 cells/l blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ ionomycin or the V␦2 ␥␦ T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of ␥␦ T cells in their peripheral blood than humans did. Following stimulation, ␥␦

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

“…They addressed this issue by administering IFN-a to eight sooty mangabeys for approximately 4 months. 31 IFN-a transiently lowered viral load early in the chronic infection of the nonpathogenic model. While slight increases in T cell activation markers were observed transiently, they were down-modulated, leading to the conclusion that IFN-a alone is unlikely to induce chronic immune activation or progression to a pathogenic phenotype in the natural hosts.…”

Effect of Highly Active Antiretroviral Therapy on T-Cell Sub-population Profile in Human Immunodeficiency Virus-1 Infected Patients

“…The comparative study done on following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys also shows that the levels of the production of the two sub population of ϒδ T cells cytokines did vary [14]. For example, when Vδ2 ϒδ T cells from uninfected donors were stimulated with protease inhibitor (PI) antigen, nearly 90% of the cells expressed TNF-α compared to 60% expressing IFN-γ.…”

“…For example, when Vδ2 ϒδ T cells from uninfected donors were stimulated with protease inhibitor (PI) antigen, nearly 90% of the cells expressed TNF-α compared to 60% expressing IFN-γ. The increased expression of TNF-α suggests that ϒδ T cells may preferentially express this cytokine for the potential killing of HIV/SIV-infected cells or modulating the immune system in response to opportunistic pathogens [14].…”

“…Concerning about ϒδ T cells, there are two main ϒδ T -cell subsets that express either the first variable region (Vϒδ1) or the second variable region (Vϒδ 2) of the delta locus from the T-cell receptor (TCR) [16]. The Vδ1 ϒδ T cells are found predominately at mucosal sites and can respond to nonclassical major histocompatibility complex molecules expressed on stressed cells, while V δ2 ϒδ T cells are predominately in the peripheral circulation and respond to non peptide phosphor antigens [14].…”

“…ϒδ T cells population are minor constituents in the peripheral blood but provide a high contribution to the immune compartment of the gastrointestinal mucosa [13], likely representing the first defense against pathogens crossing this surface. In the mucosa, they constitute up to 50% of all lymphocytes population and approximately 10% of lymphocytes in the lamina propria [14][15][16].…”