In vitro responses to Leishmania antigens by lymphocytes from patients with leishmaniasis or Chagas' disease.

Abstract

T cell responses are correlated with recovery from and resistance to leishmaniasis. Antigens of Leishmania chagasi were evaluated by determining their ability to elicit in vitro proliferation and cytokine production in peripheral blood lymphocytes and in T cell lines and clones from patients with histories of leishmaniasis or Chagas' disease. Antigens tested were selected by their reactivity with patient antibodies. Several of the antigens induced proliferative responses in peripheral blood lymphocytes from patients recovered from visceral or cutaneous leishmaniasis or with chronic Chagas' disease. Two purified glycoproteins, 30 and 42 kD, were consistently among the most effective in eliciting high proliferative responses and IL-2 production. Lymphocytes from a recovered visceral leishmaniasis patient were used to produce T cell lines against either the 30-or 42-kD antigen. Each of the lines responded to both of these antigens as well as to crude leishmania lysate. Cb4+ T cell clones specific for either or both of these antigens were also isolated from a visceral leishmaniasis patient. In contrast, rabbit antisera produced against these two antigens were not crossreactive. Both antigens were effective in inducing the production of IFN-'y from T cell lines from both leishmaniasis and Chagas' disease patients. These studies demonstrate the potential for defining parasite antigens with broad immunostimulatory capabilities. (J. Clin. Invest. 1990. 85:690-696.) leishmania * antigens -T cells * leishmaniasis

Potential role for interleukin-10 in the immunosuppression associated with kala azar.

“…The diminished IFN-'y release in the presence of CD8 + cells could be reversed by the addition of neutralizing IL-1O antibody. Together, these data support a possible role for IL-10 in mediating the immunosuppression of acute kala azar and suggest complex interactions between CD8+ and CD4' cells in determin- ( 17) and L. donovani ( 18). These studies together with a number of investigations of murine L. major infection (5, 6) have established the central role for CD4 + Th 1 cells in elaboration of macrophage-activating factors implicated in eradication of the parasite ( 19).…”

“…These studies together with a number of investigations of murine L. major infection (5, 6) have established the central role for CD4 + Th 1 cells in elaboration of macrophage-activating factors implicated in eradication of the parasite ( 19). As noted by others ( 17,18), cloning of human cells by the methods used led to an outgrowth of CD4' cells that was readily maintained in culture. Although most of the macrophage-activating clones also released IFN-'y and LT, this was not an invariant response, suggesting other mechanisms, including cytotoxicity (20), might underlie host defense against leishmania.…”

“…All were from the state of Ceara in northeastern Brazil, where kala azar is endemic (8). Two adults males, 17 and 39 yr old (designated D4 and D5), were skin test positive to L. chagasi antigens using reagents and criteria previously described (8). Peripheral blood lymphocytes from both men proliferated and released IFN--y in response to L. chagasi antigens in vitro, and activated autologous infected macrophages to kill intracellular amastigotes in vitro (2).…”

“…Neither had any signs or symptoms attributable to L. chagasi infection at the time of study or had any history of kala azar. Two adult males, 17 and 33 yr old (designated R2 and R8), were treated for kala azar upon presentation with typical signs and symptoms and demonstrable amastigotes in biopsies of bone marrow. Both received 20 d of therapy with pentavalent antimony (20 mg/kg per d) and neither required retreatment.…”

T Cell Response of Asymptomatic Leishmania chagasi Infected Subjects to Recombinant Leishmania Antigens

“…Several antigens have been isolated from different leishmania species. These antigens are recognized by serum from VL patients (Schreffler et al 1993) and by T cells from patients cured of VL or with cutaneous or mucosal leishmaniasis (Reed et al 1990). However the ab-sence of good experimental model for L. chagasi infection have limited identification of antigens able to induce a protective immune response.…”