Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal

Abstract

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.

FIG. 1.

HIV IFN-γ Elispot response profile of PBMC from an HIV-2-infected patient. The bars depict the average number of IFN-γ spot-forming cells (SFC) per 10⁶ PBMC. (A) Initial mapping of the HIV-specific T-cell responses with peptide pools spanning Gag, Env, Nef, and Tat of HIV-1 and HIV-2. For HIV-1, there are five Gag peptide pools (pool 1, peptides spanning amino acids 1 to 110; pool 2, 100 to 210; pool 3, 200 to 310; pool 4, 300 to 410; pool 5, 400 to 495); nine Env pools (pool 1, 1 to 110; pool 2, 100 to 210; pool 3, 200 to 310; pool 4, 300 to 410; pool 5, 400 to 510; pool 6, 500 to 610; pool 7, 600 to 710; pool 8, 700 to 810; pool 9, 800 to 861); two Tat pools (pool 1, 1 to 65; pool 2, 55 to 101), and four Nef pools (pool 1, 1 to 65; pool 2, 55 to 120; pool 3, 110 to 175; pool 4, 165 to 209). For HIV-2, there are five Gag pools (pool A, 1 to 110; pool B, 100 to 210; pool C, 200 to 310; pool D, 300 to 410; pool E, 400 to 522); nine Env pools (pool A, 1 to 110; pool B, 100 to 210; pool C, 200 to 310; pool D, 300 to 410, pool E, 400 to 510; pool F, 500 to 610; pool G, 600 to 710; pool H, 700 to 810; pool I, 800 to 858); two Tat pools (pool A, 1 to 75; pool B, 65 to 130), and four Nef pools (pool A, 1 to 65; pool B, 55 to 120; pool C, 110 to 175; pool D, 165 to 256). Phytohemagglutinin (PHA)-stimulated cells served as the positive control (not shown), and cells stimulated with no peptides served as the negative control. (B) Determination of the T-cell subset (CD4⁺ or CD4⁻) responsible for IFN-γ secretion and recognition of the individual 20-mer peptides within HIV-2 Gag pool C.

FIG. 2.

Frequency and magnitude of T-cell responses to HIV peptides recognizing epitopes within Gag, Env, Nef, and Tat. (A) Frequency of homologous T-cell responses recognizing HIV Gag, Env, Nef, and Tat (i.e., responses to HIV-1 Gag, Env, Nef, and Tat in HIV-1-infected patients, and responses to HIV-2 Gag, Env, Nef, and Tat in HIV-2-infected patients). (B) Magnitude of homologous T-cell responses. (C) Frequency of cross-reactive T-cell responses to HIV Gag, Env, Nef, and Tat in HIV-1- and HIV-2-infected patients (i.e., responses to HIV-2 Gag, Env, Nef, and Tat in HIV-1-infected patients, and responses to HIV-1 Gag, Env, Nef, and Tat in HIV-2-infected patients). (D) Magnitude of cross-reactive T-cell responses to HIV Gag, Env, Nef, and Tat in HIV-1- and HV-2-infected patients.