Depletion of pro-inflammatory CD161+ double negative (CD3+CD4−CD8−) T cells in AIDS patients is ameliorated by expansion of the γδ T cell population

Abstract

In this present investigation, flow cytometry was utilized to evaluate 13 healthy controls and 31 HIV-1 infected patients who had advanced to the AIDS stage of infection (CD4 count below 200cells/mm3), for the expression of CD161 on CD3+ double negative (DN) (CD3+CD4-CD8-) T cells, CD4+ T cells, CD8+ T cells and γδ T cells. The observed depletion of CD161+ T cells from peripheral circulation was due primarily to the loss of CD4+CD161+ T cells; as these cells represented 8.67±0.74% of the total healthy control peripheral T cell population, while the CD4+CD161+ T cells of the AIDS group represented only 3.35±0.41% (p=<0.0001) of the total peripheral T cell population. We have also shown here that the DN T cell population was more than doubled in the AIDS group, with the DN T cell population expanding from 3.29±0.45% of the healthy control peripheral T cell population to 8.64±1.16% (p=0.0001) of the AIDS group peripheral T cell population. By evaluating the expression of CD161 on the surface of the DN T cells we showed that within the healthy control group, 47.4±4.99% of the DN T cells were positive for the expression of CD161, while only 26.4±3.54% (p=0.002) of the AIDS group's DN T cells expressed CD161. Despite CD161 expression being halved on the DN T cells of the AIDS group, when we compared the total peripheral T cell percentage of CD161+ DN T cells between the healthy control group and the AIDS group, there was no statistical difference. Even though only 26.4% DN T cells within the AIDS group were positive for CD161+, the overall DN T cell population had expanded to such an extent that there was no statistical difference between the groups with regard to CD161+ DN T cells as a percentage of the total peripheral T cell population. Furthermore, we showed that within the DN T cell population, there was an approximate 2:1 ratio of γδ to αβ T cells, and this ratio was maintained in both the healthy control group and the AIDS group. While evaluating γδ T cells we also discovered that CD8+ γδ T cells were expanded from 0.62±.09% of the healthy control peripheral T cell population to 5.01±.88% (p=<0.0001) of the peripheral T cell population of the AIDS group; and that this population of CD8+ γδ T cells underwent the same reduction in percentage of cells expressing CD161+, further demonstrated that the phenomenon of CD161+ percentage reduction and compensatory increase in total cell population was affecting the entire circulating γδ T cell population.