T-cell receptor Vβ repertoire of CD8+ T-lymphocyte subpopulations in cutaneous leishmaniasis patients from the state of Rio de Janeiro, Brazil

Abstract

In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+T-cells are associated with larger lesions.

CD3+CD4negCD8neg (double negative) T lymphocytes and NKT cells as the main cytotoxic-related-CD107a+ cells in lesions of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis

“…Flow cytometry (FCM) has been extensively applied as a key method to address these issues, and the majority of the reports are based on peripheral-blood-sample analysis [6, 11, 28–30]. However, it is known that lymphocytes are recruited from blood to lymph nodes, primed with antigens and then migrate to lesion sites; consequently, frequencies of antigen-specific T cells are higher in leishmaniasis lesions than in blood [7, 17, 31, 32].…”

“…Previous in situ immunopathological studies using confocal or fluorescent microscopy techniques in leishmaniasis have improved our expertise with the description of the cellular composition of the skin inflammatory infiltrate [ 18 , 23 , 24 , 26 , 27 ]. Flow cytometry (FCM) has been extensively applied as a key method to address these issues, and the majority of the reports are based on peripheral-blood-sample analysis [ 6 , 11 , 28 – 30 ]. However, it is known that lymphocytes are recruited from blood to lymph nodes, primed with antigens and then migrate to lesion sites; consequently, frequencies of antigen-specific T cells are higher in leishmaniasis lesions than in blood [ 7 , 17 , 31 , 32 ].…”

T-cell receptor variable region usage in Chagas disease: A systematic review of experimental and human studies

“…This indicates that the TCR Vβ subfamilies in the cardiac lesion of Chagas individuals are less restricted, but more studies are needed to evaluate the alpha chain of the TCR heterodimer. In Leishmania infection, a higher variability was observed in TCR Vβ usage, as compared to Vα [60][61][62][63]. This more restricted Vα region can be explained by the fact that somatic recombination of the TCR alpha chain occurs only between subregions V (variability) and J (junction).…”

Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients

“…In a second vein, HIV-positive patients evolve with disturbances in the generation of the T lymphocyte receptor Vβ repertoire (TCRVβ) (17), which can potentially compromise the effector responsiveness to a variety of antigens, including Leishmania. In this context, disorders of the TCRVβ repertoire have been related to the immunopathogenesis of several diseases, such as cancer (22); rheumatoid arthritis (23); hematological comorbidities (24); Chagas disease (25); cutaneous leishmaniasis (26,27); and HIV/AIDS (28,29). HIV-positive patients with a restrict mono-oligoclonal TCRVβ repertoire profile present a rapid AIDS-progression, suggesting that the T-cell repertoire disturbances do influence the HIV/AIDS prognosis (28) and of its association with other infections, such as Epstein Barr virus (30).…”