Clinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is not known and in vivo studies on T-cell function may provide valuable information. Nevertheless, there are limited studies on the nature of the stimulatory effects of live vs. killed parasites on human T cells in vitro. A total of nine Leishmanin Skin Test+ volunteers with a history of self-healing CL (HCL) and seven healthy volunteers were included in this study. 5,6-carboxyfluroescein diacetate succinimidyl ester-labelled CD4(+)/CD8(+) lymphocytes were cultured with killed Leishmania Lysate (Killed LL) or live Leishmania major (Live LM) and analysed for proliferation using flow cytometry. Culture supernatants were used for cytokine titration. In HCL volunteers, upon stimulation with killed LL, the number of proliferated CD4(+)/CD8(+) cells was significantly more than that of unstimulated (P < 0.001) or live LM stimulated (P < 0.05) cells, or cells from controls (CD4(+)/CD8(+): P < 0.05/P < 0.001). Stimulation of CD4(+) cells with Live LM (P < 0.001) or Killed LL (P < 0.05) induced a significantly higher IFN-gamma production compared with that of controls, but Live LM induced significantly (P < 0.05) more IFN-gamma than Killed LL. A significantly (P < 0.05) higher IFN-gamma production was observed when CD8(+) cells were stimulated with Live LM. Cells from HCL volunteers showed significantly more IL-10 production to Live LM stimulation compared with that of controls (CD4(+): P < 0.05 /CD8(+): P < 0.001) or cells stimulated with Killed LL (CD4(+)/CD8(+): P < 0.001/P < 0.0005). Whereas Killed LL induced more proliferation response in purified T cells, Live LM induced cytokine production without significant induction of proliferation. The results from healed CL volunteers in this study could be implicated in further studies on T-cell response in vaccinated individuals.
Various Leishmania antigens showed to induce protection when used with IL-12 as an adjuvant in an animal model of leishmaniasis. Limitations in using IL-12 justify searching for an appropriate adjuvant to accelerate induction of a Th1-type immune response and protection. In this study, the role of Mycobacterium vaccae as an adjuvant mixed with either autoclaved Leishmania major (ALM) or freeze-thawed-killed L. major (KLM) in increasing protection in susceptible and resistant mice was studied. Nineteen groups of BALB/c and 19 groups of C57BL/6 mice, ten mice per group, were immunized three times in 45 days interval with different doses of either KLM or ALM alone or mixed with either BCG or different doses of M. vaccae. Immunized groups of mice and PBS-injected control group were challenged with 2 x 10(6) promastigotes of L. major at the base of the tail. The evolution of the lesion was monitored, and the size of the lesion was measured and recorded weekly. Anti-Leishmania total IgG Ab was titrated before and after challenge. The results showed that immunization of either susceptible or resistant mice with KLM or ALM mixed with low dose of M. vaccae increased protection defined by significantly smaller ulcer size in immunized mice compared with the PBS-injected control group.
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