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

Human 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.

Fig. 2

Proportion of natural killer T (NK T) cells in patients and controls. The NK T cell frequencies of three subject groups is shown from the American cohort (a) (black dots) and Brazilian cohort (b) (white dots). Absolute numbers of NK T cells for the American cohort (c) (black dots) and Brazilian cohort (d) (white dots).

Fig. 1

Gating strategy for the natural killer T (NK T) cells. Gating strategy for NK T cells from the (a) San Francisco HTLV Outcomes Study (HOST) cohort and (b) Sao Paulo cohort. One representative donor from each cohort is shown.

Fig. 3

Proportion of natural killer T (NK T) cell subsets in patients. The frequencies of total (a) NK T cell lymphocyte subsets and (b) CD3⁺ cells expressing single positive (SP) CD4 and CD8 cells together with CD4^-/CD8^- double negative (DN) cells from the Brazilian cohort. (c,d) The frequency of NK T cells from two time-points in 10 human T lymphotropic virus type 1 (HTLV-1) infected individuals; HTLV-1 carriers (c) and those with HAM/TSP (d) from the Brazilian cohort. *P < 0·05 statistically significant.