Compensation for Decreased Expression of B7 Molecules onLeishmania infantum-Infected Canine Macrophages Results in Restoration of Parasite-Specific T-Cell Proliferation and Gamma Interferon Production

Infection and Immunity - Tập 67 Số 1 - Trang 237-243 - 1999
Elena Pinelli1, Victor P. M. G. Rutten1, Martijn Bruysters1, Peter F. Moore2, E. J. Ruitenberg3,1
1Department of Immunology, Faculty of Veterinary Medicine, 3584 CL Utrecht,1 and
2Department of Veterinary Pathology, School of Veterinary Medicine, University of California, Davis, California 95616-87392
3Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam,3 The Netherlands, and

Tóm tắt

ABSTRACTInfection of humans and dogs byLeishmania infantummay result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts ofLeishmaniaparasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection withL. infantumaffects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-γ) production by aLeishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-γ, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.

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Tài liệu tham khảo

Ashford R. W. Bettini S. Ecology and epidemiology: Old World Leishmaniasis in biology and medicine. Peters W. Killick-Kendrick R. 1987 365 424 Academic Press Inc. New York N.Y

10.1126/science.1636092

10.1016/0167-5699(92)90138-W

10.1111/j.1365-3024.1992.tb00026.x

Carvalho E. M. Teixeira R. S. Johnson W. D. Jr. Cell-mediated immunity in American visceral leishmaniasis.Infect. Immun.481981409414

Chakkalath H. R. Titus R. G. Leishmania major-parasitized macrophages augment Th2-type T cell activation.J. Immunol.153199443784387

10.1002/eji.1830221207

10.1111/j.1399-0039.1985.tb00448.x

10.1084/jem.174.3.625

Fruth U. Solioz N. Louis J. A. Leishmania major interferes with antigen presentation by infected macrophages.J. Immunol.150199318571864

10.1016/0165-2427(92)90181-O

10.1128/iai.42.2.702-707.1983

10.1038/icb.1979.2

Ho M. Koech D. K. Iha D. M. Bryceson A. D. M. Immunosuppression in Kenyan visceral leishmaniasis.Clin. Exp. Immunol.511983207214

10.1016/0167-5699(92)90137-V

10.1002/eji.1830241140

10.1128/iai.61.3.1069-1073.1993

10.1016/S0065-308X(08)60208-0

10.1084/jem.173.3.721

10.1084/jem.174.3.561

10.1111/j.1365-3024.1993.tb00635.x

Moore P. F. Rossitto P. V. Development of monoclonal antibodies to the canine T cell receptor complex (TCR/CD3) and their utilization in the diagnosis of T cell neoplasia.Vet. Pathol.301993457

Moore P. F. Rossitto P. V. Olivry T. Development of monoclonal antibodies to canine T cell receptor-1 (TCR-γδ) and their utilization in the diagnosis of epidermotropic cutaneous T cell lymphoma.Vet. Pathol.311994597

Murphy M. L. Engwerda C. R. Gorak P. M. A. Kaye P. M. B7-2 blockade enhances T cell responses to Leishmania donovani.J. Imunnol.159199744604466

10.1016/0923-2494(91)90105-R

10.1007/BF01262330

10.1111/j.1399-0039.1994.tb02321.x

10.1128/iai.62.1.229-235.1994

10.1002/eji.1830250619

Prina E. Jouanne C. de Souza Lao S. Szabo A. Guillet J.-G. Antoine J.-C. Antigen presentation capacity of murine macrophages infected with Leishmania amazonensis amastigotes.J. Immunol.151199320502061

10.1002/eji.1830271024

Reiner N. E. Parasite-accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus-dependent suppression of macrophage interleukin 1 response by Leishmania donovani.J. Immunol.138198719191925

Reiner N. E. Winnie N. G. McMaster W. R. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products.J. Immunol.138198719261932

10.1084/jem.179.2.447

Sacks D. L. Lal S. L. Shrivastava S. N. Blackwell J. Neva F. A. An analysis of T cell responsiveness in Indian kala-azar.J. Immunol.1381987908913

10.1002/eji.1830250913

Snyder D. S. Lu C. Y. Unanue E. R. Control of macrophage Ia expression in neonatal mice—role of a splenic suppressor cell.J. Immunol.128198214581465

10.1038/333850a0

10.1002/eji.1830210719

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Infection and Immunity

Tập 67 Số 1

237-243

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