Potential role for interleukin-10 in the immunosuppression associated with kala azar.
Patients with acute kala azar are generally nonreactive in a number of immunologic assays, including T cell proliferation and generation of macrophage-activating cytokines, principally IFN-gamma, in response to leishmania antigens in vitro. To test for potential immunosuppressive factors, a series of T cell lines and clones were established from patients with acute kala azar, from patients after chemotherapy for kala azar, and from skin test-positive adults from the same endemic region. Although CD4+ T cell lines and clones could be readily established from the skin test-positive adults, lines and clones from acute or treated patients were heavily biased in expression of CD8+. The CD8+ cells from acute patients did not themselves release cytokines in response to leishmania antigens in vitro, but markedly affected the cytokine profile of peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition of the CD8+ cells caused inhibition of lymphoproliferation and IFN-gamma release, with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+ cells could be partially abrogated by antibodies to IL-10 but not by antibodies to IL-4. Analysis of four patients with acute kala azar demonstrated release of IL-10 that could not be demonstrated in supernatants from asymptomatic skin test-positive individuals. Generation of IL-10 may contribute to the profound suppression of IFN-gamma release that occurs during kala azar due to Leishmania chagasi.
Holaday
B J
BJ
Department of Medicine and Microbiology/Immunology, University of California, San Francisco School of Medicine 94143.
Pompeu
M M
MM
Jeronimo
S
S
Texeira
M J
MJ
Sousa
A de A
Ade A
Vasconcelos
A W
AW
Pearson
R D
RD
Abrams
J S
JS
Locksley
R M
RM
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012882:Skin Tests; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D015850:Interleukin-6; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate