A Significant Number of Human Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes Detected by Tetramer Binding Do Not Produce Gamma Interferon

Abstract

Despite the seemingly important role of cytotoxic T-lymphocyte (CTL) responses in human immunodeficiency virus (HIV) disease pathogenesis, their measurement has relied on a variety of different techniques. We utilized three separate methodologies for the detection of CTLs in a cohort of HIV-infected individuals who were also human leukocyte antigen A2 (HLA-A2) positive. Among the different CTL assays, a correlation was seen only when the Gag epitope-specific HLA A*0201-restricted tetramer assay was compared with the ELISPOT assay performed after stimulation with the Gag epitope; however, this correlation was of borderline statistical significance. On average, the tetramer reagent detected a 10-fold-higher number of cells than were seen to produce gamma interferon by the ELISPOT assay. The implications of this CTL assay comparison and the possibility of phenotypic differences in HIV-specific CD8 ؉ T lymphocytes are discussed.

Presence of HIV-1 Gag-Specific IFN-γ+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection

“…In 10 LTNPs and 7 SPs, frequencies of IFN-␥ ϩ CD4 and CD8 T cells were enumerated in the same sample. CD8 T cell IFN-␥ frequencies did not differ between LTNPs and SPs, and ranged from 0.00 to 1.04% with a median of 0.24% in all 17 subjects, which is consistent with several others reports (35)(36)(37)(38) where Gag-specific CD8 IFN-␥ ϩ frequency was measured by either the ICS or the ELISPOT assay. Data in Fig.…”

Differential role of IL‐2R signaling for CD8+ T cell responses in acute and chronic viral infections

“…While percentages of total IL-2Ra +/+ CD8 + T cells increased 7-to 8-fold in both test and control chimeras 8 days after infection, percentages of total IL-2Ra -/-CD8 + T cells increased only 2-fold (not shown). Expansion of LCMV gp [33][34][35][36][37][38][39][40][41] (gp33)-specific CD8 + T cells was assessed in blood, spleen, liver and lung by tetramer staining. Frequencies of specific T cells were comparable within the IL-2Ra -/-CD8 + T cell compartment and the control CD8 + T cell compartment: roughly 13% of Ly5.2 + (IL-2Ra -/-) as well as of wildtype Ly5.1 + CD8 + T cells were specific for the LCMVderived epitope gp33 (Fig.…”

“…6B). Dysfunction of virusspecific CD8 + T cells with respect to cytokine production but to a lesser extent with respect to degranulation seems to be common during high-level chronic viral infection ( [29][30][31][32][33][34][35][36][37] and Agnellini et al, unpublished observations).…”

“…Transgenic mice expressing a TCR specific for LCMV peptide gp [33][34][35][36][37][38][39][40][41] were described previously [56]. Ly5.2 + C57BL/6 mice were purchased from Janvier, and Ly5.1 + C57BL/6 and IL-2Ra -/-mice were purchased from Jackson and were maintained in a specific pathogen-free (SPF) facility.…”

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

“…Cytokine secretion can be limited by the T cell exhaustion state 12, 32 during chronic viral infections 33, 34, malignant tumors 35, and parasitic diseases 36. Chronic chagasic patients displayed dysfunctional T cell responses characterized by increased frequency of terminally differentiated cells, monofunctional antigen‐specific T cell responses and progressive attenuation of cytokine production 7, 10, 21, 37.…”