Determinants of HIV-specific CD8 T-cell responses in HIV-infected pediatric patients and enhancement of HIV-gag-specific responses with exogenous IL-15.
Cellular immune responses play a central role in controlling HIV-1 infection. HIV-specific IFN-gamma production by CD8 T cells was evaluated in 17 HLA-A2+ HIV-infected pediatric patients (age range 1 month to 16 years) in an ELISPOT assay. Most patients (15/17) exhibited responses to HIV-gag, followed by responses to envelope gp120, gp41, and V3 loop. Only 7 patients responded to all four antigenic peptides. Treatment-related immune reconstitution of CD4 T cells was associated with increase in gag-specific responses, but these declined with prolonged viral suppression. Exogenous IL-15 resulted in augmentation of HIV-gag-specific response in 71% of patients, while IL-2 and IL-7 had variable effects, augmenting responses in 25% patients. Thus, HIV-specific CD8 T-cell responses are dependent on both CD4 T-cell help and antigenic stimulation. The cytokine IL-15 may be a useful modality as adjunctive therapy to augment HIV-specific memory CD8 T cells.
Immunology and Inflammation Center of Excellence, North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA.
Vivek
V
Chitnis
Rajendra
R
Pahwa
Savita
S
Pahwa
D000293:Adolescent; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D019409:Interleukin-15 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019562:Viral Load
D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D019409:Interleukin-15; D007371:Interferon-gamma