Disparate immunoregulatory potentials for double-negative (CD4- CD8-) αβ and γδ T cells from human patients with cutaneous leishmaniasis

Although most T lymphocytes express the alpha beta T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4(-) CD8(-) (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing up or gamma delta T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the up T-cell receptor, with the remainder expressing the gamma delta receptor, while healthy donors displayed the opposite distribution with similar to 75% of the DN T cells expressing the gamma delta T-cell receptor. Additionally, up DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while alpha beta DN T cells from Leishmania-infected individuals present a proinflammatory cytokine profile, gamma delta DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.