CD45RO+ T Cells and T Cell Activation in the Long-Lasting Immunity after Leishmania infantum Infection

Abstract

Manifestations of Leishmania infantum infection range from asymptomatic to symptomatic visceral leishmaniasis (VL). People with symptomatic VL (sVL) have suppressed immune responses against Leishmania antigens that are reversed after clinical cure. The intradermal leishmanin skin test (LST) is negative during sVL, but it becomes positive after treatment. The aim of this study was to compare T cell responses in individuals with sVL, recovered VL (RecVL), and endemic controls. Endemic controls were household contacts of a VL case and they were grouped by their LST results, either positive (LST+) or negative (LST-). Mononuclear cells were studied ex vivo or after stimulation with soluble Leishmania antigens (SLA); cell surface markers and cytokines were determined. T cells, ex vivo, from individuals with sVL and from LST+ individuals presented a higher activation for CD4⁺ and CD8⁺ cells expressing CD69. However, lymphocytes from sVL stimulated with SLA had lower percentages of CD4⁺ and CD8⁺ cells expressing CD69 and CD8⁺ cells expressing CD25, with no release of interferon-γ or tumor necrosis factor. sVL subjects had lower percentage of memory cells (CD4⁺ CD45RO+), ex vivo, without SLA stimulation than RecVL, LST+, or LST- (P = 0.0022). However, individuals with sVL had fewer regulatory cells after SLA stimulation (CD4⁺ CD25^HIGH, P = 0.04 and CD4⁺ FOXP3+, P = 0.02) than RecVL. The decrease in specific memory and activated CD4⁺ and CD8⁺ cells, as in response to Leishmania antigens, could explain, in part, the immune impairment during sVL. Finally, protective T cell responses are long lasting because both RecVL or LST+ individuals maintain a specific protective response to Leishmania years after the primary infection.