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Abstract: A prospective study on 23 patients with American visceral leishmaniasis (VL), comparing clinical and laboratory parameters of 14 children (mean age of 3.85±3.39 years) to nine adults (27.4±10.90 years) was performed in São Luís, Maranhão, Brazil, between August 2000 and July 2002. Data were collected at entrance (day 0), end of treatment, as well as 120 and 210 days after treatment using a protocol chart containing patient identification, clinical and laboratory data. N-Methylglucamine antimonate administered at the dose of 20mg/Sb5+/kg/day for 20–30 days was successfully used in all patients. Patients were followed for 1 year after treatment, and no relapses were observed. A prolonged duration of the disease, lymphadenopathy and bleeding predominated in adult patients, while hepatomegaly and skin-mucosal pallor were more frequent in children. Disease was longer and more severe in adults than in children. Although both groups exhibited a trend toward normalization of hematological and biochemical parameters, more children returned sooner to normal values than adults. Difference in clinical or laboratory parameters between children and adults did not indicate the need for different clinical or therapeutic approaches. [Copyright &y& Elsevier]

Crucial to the defense against leishmaniasis is the ability of the host to mount a cell-mediated immune response capable of controlling and/or eliminating the parasite. Cell recruitment to the site of infection is essential to the development of the host cellular immune response. The process is controlled by chemokines, which are chemotactic cytokines produced by leukocytes and tissue cells. [Copyright &y& Elsevier]

Abstract: T cell-mediated immunity is critical in resistance against Leishmania parasites, and T cell activation requires signals provided by costimulatory molecules. Herein we evaluated the role of costimulatory molecules on cytokine production and T cell surface molecule expression by peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis (CL) patients. PBMC from CL patients were stimulated with soluble Leishmania antigen (SLA, 10 μg/ml), in the presence or absence of soluble CTLA4-Ig to block CD28-B7 interaction or in the presence or absence of anti-human CD40L to block CD40-CD40L interaction. Supernatants were harvested to evaluate tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and interferon gamma (IFN-γ) production by ELISA. Cells were harvested after 48 h of culture, stained for specific activation markers and analyzed by flow cytometry. Results show that the blockade of CD28-B7 interaction by CTLA4-Ig downmodulated IFN-γ, IL-10, and TNF-α secretion by PBMC from CL patients. No alteration was detected on either TGF-β production or the expression of CTLA44 or CD25 on CD4+ and CD8+ T cells. When the CD40-CD40L interaction was blockade using anti-CD40L, we did not observe changes in cytokine production or in surface molecule expression. The blockade of the CD28-B7 interactions by CTLA4-Ig also did not alter cytokine production in volunteers immunized against tetanus toxoid (TT). Taken together, these data suggest that the interaction of CTLA4 and CD28-B7 is a TGF-β-independent mechanism that specifically downmodulates the immune response in cutaneous leishmaniasis patients. [Copyright &y& Elsevier]

Adhesion molecules play a crucial role in cell migration and recruitment. Expression of adhesion molecules that preferentially address cells to inflammatory sites is a critical event in the formation and maintenance of leishmaniasis lesions. In this work, we analyzed the expression of CD11a, CD11b and CD62L, adhesion molecules involved in cell activation and circulation, in CD4+ and CD8+ T cells from peripheral blood and lymph nodes of patients with early cutaneous leishmaniasis. The percentage of expression of CD62L, CD11a and CD11b in total lymphocytes was lower in lymph nodes as compared to peripheral blood. Moreover, differences in adhesion molecule expression between blood and lymph nodes were more striking in CD4+ than CD8+ T cells. Stimulation of PBMC from leishmaniasis patients with soluble Leishmania antigens (SLA) lead to the expansion of CD4+CD62Lhigh cells, CD4+CD11b+ cells and to an increase in the intensity of expression of CD11a in CD4+, but not CD8+ T cells. Our data suggest that early activation events that occur in the lymph nodes of patients recently infected with Leishmania lead to changes in T cell adhesion molecule expression, favoring migration to the periphery and increasing the likelihood of further recruitment to lesion sites. [Copyright &y& Elsevier]

A correction to the article "CD8+ Granzyme B+-Mediated Tissue Injury versus CD4+IFNγ+-Mediated Parasite Killing in Human Cutaneous Leishmaniasis" by Claire da Silva Santos and colleagues is presented.