Natalia Olaya

Increased CD4+/CD8+ Double-Positive T Cells in Chronic Chagasic Patients

Background CD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out. Methodology/Principal Findings Seventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1%±0.9) compared with healthy (1.1%±0.5) and non-chagasic cardiomyopathy (1.2%±0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor. Conclusions Chagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm2) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

Reporte de casoProliferación linfoide indolente cutánea CD8 positiva a propósito de tres casos con compromiso facialIndolent CD8-positive t-cell lymphoid proliferation: on purpose three cases of facial commitment

Primary cutaneous indolent CD8-positive lymphoid proliferation is a recent variant of cutaneous T lymphoma that is characterized by nodule, papule or plaque erythematous with slow growth that can affect the facial or extrafacial region. In the histopathology study it is characterized by an infiltration of monomorphic T lymphocytes throughout the dermis with presence of Grenz zone and absence of epidermotropism. The infiltrate is characteristically CD 8+ and CD3 + TIA-1 + CD4-, CD56- CD30, PD-1, Granzyme B- and negative EBER. Ki-67 proliferation index is less than 10% and clonal T-cell receptor gene rearrangements. Clinical follow-up is favorable and has not been observed systemic involvement. We present three cases with facial involvement (two cases in ear and one case with nasal commitment) with typical clinical presentation, histopathological findings (curiously a case with clear cell change) and clonality studies.