Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

Abstract

SummaryHuman T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/ TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4 + and fewer CD8 + cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4 + NK T subset are associated with HTLV-1 disease progression.

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

“…We did not observe any difference in frequency of MAIT cells between asymptomatic carriers and HAM/TSP patients. This is in contrast with what has been reported for iNKT cells, another subset of innate T cells, that were further reduced in HAM/TSP patients[17, 40]. …”

“…The high frequency of HTLV-1-specific IFN-γ-producing CD4+ and CD8+ T cells in the central nervous system (CNS) and in peripheral blood seen in HAM/TSP patients suggest that T-cell responses do not prevent development of disease, contributing instead to the proinflammatory milieu characteristic of HTLV-1 related syndromes[14–16]. Other T-cell subsets such as NKT cells were investigated in the context of HTLV-1 infection[17], but many aspects of the immunopathogenesis of HTLV-1 related diseases and why HTLV-1 patients are more susceptible to Mtb are still unexplored.…”

Role of killer cell immunoglobulin-like receptor gene content and human leukocyte antigen–C group in susceptibility to human T-lymphotropic virus 1–associated myelopathy/tropical spastic paraparesis in Peru

“…In fact, it has been reported that HTLV-1-infected HAM/TSP patients have lower numbers of NK cells [9] and a decreased activity of NK cells in comparison with ACs [10,11].…”

Lower numbers of natural killer T cells in HIV‐1 and Mycobacterium leprae co‐infected patients

“…Diminished NKT cell‐mediated anti‐tumour responses could also contribute to increased incidence of infection‐related tumours such as Kaposi sarcoma and non‐Hodgkin’s lymphoma in AIDS patients 24 . In another human retrovirus infection, lower numbers of circulating Vα24 + Vβ11 + NKT cells in individuals infected with human T lymphotropic virus type 1 (HTLV‐1) have been demonstrated 31 …”