Progressive expansion of an L-selectin-negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats
ABSTRACT The acute stage of feline immunodeficiency virus (FIV) infection is characterized by the appearance of a major CD8 subpopulation with reduced expression of the CD8 beta chain (CD8alpha+betalo). CD8 antiviral activity was subsequently shown to be mediated by the CD8alpha+betalo phenotype, which is the dominant CD8 phenotype in long-term infected cats. Two- and three-color flow cytometric analysis demonstrated that the CD8alpha+betalo subset is L-selectin negative (CD62L-) and has increased expression of CD44, CD49d, and CD18, consistent with an activation phenotype. The CD8alpha+betaloCD62L- cells but not the CD8alpha+betahiCD62L+ cells demonstrated strong antiviral activity in the FIV acute-infection assay. The progressive expansion of the CD8alpha+betaloCD62L- effector subset cells in FIV-infected cats parallels that seen in human immunodeficiency virus (HIV)-infected patients, suggesting that failure in homeostatic mechanisms regulating lymphocyte activation or trafficking (or both) may be a consequence of both HIV and FIV infections.
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ABSTRACT: Tumor infiltrating lymphocytes (TIL) reflect the host's anti-tumor immune response, and can be a valuable predictor of prognosis. However, many properties of TIL are not fully understood. In the present study, TCR-Vβ repertoires of cancer patients were primarily analyzed by flow cytometry. Abnormally expressed TCR-Vβ subfamilies were generally found in both TIL and peripheral blood lymphocytes (PBL) of each patient. Of note, increased patient age was associated with increasingly biased TCR-Vβ repertoire in TIL but not in PBL, and the dispersion degree of the differences of TCR-Vβ subfamilies between TIL and PBL correlated positively with age (P = 0.007). Utilizing immunoscope analysis, we identified the age-related reduction in TCR-Vβ diversity, but polyclonal pattern was predominant in significantly expanded TCR-Vβ subfamilies. In addition, we found that older patients possessed a decreased ratio of CD8+CD62L+ non-effector cells in TIL compared to PBL, implying age-related increase of CD8+CD62L- effector cells in TIL. The colocalization analysis of CD8 and CD3, however, suggested the suppressed activity of these effector cells in tumor microenvironment. These findings further elucidate the properties of TIL, showing an increasing difference between TIL and PBL with age, which may provide insight for the development of effective immunotherapies for cancer patients of different ages.PLoS ONE 07/2014; 9(7):e102327. DOI:10.1371/journal.pone.0102327 · 3.53 Impact Factor
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ABSTRACT: Antibody testing based on individual risk assessments is recommended to determine feline immunodeficiency virus (FIV) status, but neither ELISA nor Western blot tests can distinguish between anti-FIV antibodies produced in response to natural infection and those produced in response to FIV vaccination. The aim of this cross-sectional study was to test the hypothesis that FIV-infected cats could be differentiated from FIV-vaccinated uninfected cats using lymphocyte subset results, specifically the CD4%:CD8low% T-lymphocyte ratio. Comparisons of the CD4%:CD8low% T-lymphocyte ratio were made among the following four groups: Group 1 - FIV-infected cats (n = 61; FIV-antibody positive by ELISA and FIV PCR positive); Group 2 - FIV-uninfected cats (n = 96; FIV-antibody negative by ELISA); Group 3 - FIV-vaccinated uninfected cats (n = 31; FIV-antibody negative by ELISA before being vaccinated against FIV, after which they tested FIV ELISA positive); and Group 4 - FIV-uninfected but under chronic/active antigenic stimulation (n = 16; FIV-antibody negative by ELISA; all had active clinical signs of either upper respiratory tract disease or gingival disease for ≥ 21 days). The median CD4%:CD8low% T-lymphocyte ratio was lower in Group 1 (1.39) than in each of the other three groups (Group 2–9.77, Group 3–9.72, Group 4–5.64; P < 0.05). The CD4%:CD8low% T-lymphocyte ratio was also the most effective discriminator between FIV-infected cats and the other three groups, and areas under ROC curves ranged from 0.91 (compared with Group 4) to 0.96 (compared with Group 3). CD4%:CD8low% shows promise as an effective test to differentiate between FIV-infected cats and FIV-vaccinated uninfected cats.Veterinary Microbiology 06/2014; 170(3-4). DOI:10.1016/j.vetmic.2014.01.014 · 2.73 Impact Factor
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