Evaluation of Cellular Immune Responses in Subjects Chronically Infected with HIV Type 1

Abstract

The importance of host cellular immune responses, particularly CD8(+) cytotoxic T-lymphocyte (CTL) responses, in control of human immunodeficiency virus type 1 (HIV-1) infection has been demonstrated in many clinical studies. These studies, along with vaccination challenge studies in rhesus macaques, indicate the importance of cellular immune responses against HIV-1. Toward this end, we evaluated anti-HIV-1 cellular immune responses in a cohort of 54 subjects who were chronically infected with HIV-1. By validation of IFN-gamma ELISpot assay, we established a dual cut-off criterion for scoring a positive response. The magnitude and frequency of cellular immune responses were measured against HIV-1 antigens (Gag, Pol, Nef, Rev, and Tat), using synthetic peptides as antigens in ELISpot assay. Here we showed that HIV-1 Gag, Pol, and Nef were frequent targets of T cell responses in these subjects, whereas Tat and Rev were less frequently recognized. We further evaluated the possible association between host cellular immune responses and corresponding plasma viral loads in this cohort. By performing ranking correlation analysis, we demonstrated a positive correlation between host viral loads and ELISpot responses of HIV Gag and Pol in untreated subjects. For the subjects under antiviral regimens, however, we did not find any significant association. Our findings suggest that the high levels of ELISpot responses in chronically infected subjects were reflective of their persistent viral infection.

Human Immunodeficiency Virus-Specific Gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point

“…The role of CD8 ϩ T cells in the initial control of viremia is well known (6,24), and there is evidence to show that in SIV-infected macaques, CD8 cells play a role in controlling viremia (19,36), although this may not necessarily be the case in the natural host of SIV (4). Most studies of HIV-infected humans have examined antigen-specific CD8 ϩ T-cell responses during chronic disease (1,10,15), and fewer studies have been performed with those controlling (5) or progressing in (37) the disease. Immunological responses in acute infection are thought to be crucial for controlling initial viral replication and may predict the subsequent viral set point.…”

Peptide Impurities in Commercial Synthetic Peptides and Their Implications for Vaccine Trial Assessment

“…Statistical analysis. In the ELISPOT assays, the cutoff for positivity was a count of Ͼ55 SFC per 1 million input PBMC and more than four times the background (mean of the negative-control wells) (12). Nonparametric tests were used for comparing the nonpaired peptide responses between the HIV-1-seronegative and -seropositive groups (Mann-Whitney rank test) and for comparing the paired peptide responses within the groups (Wilcoxon signed-rank test).…”

The Breadth of Expandable Memory CD8 + T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

“…Some proposed mechanisms include a rapid expression of epitopes derived from the Gag protein contained in the infecting viral particles and structural constraints of the Gag protein that impede CD8 ϩ T cell escape (66)(67)(68)(69)(70). However, these suggestions are inconsistent with the fact that beneficial effects of Gag-specific responses are not universal among elite controllers, and indeed, most progressors also mount detectable responses against Gag (71,72). This discrepancy can partly be explained by our recent data showing that only a subset of Gag responses, particularly those restricted by protective alleles, exhibits superior antiviral function (10).…”