Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity.
Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma production that may facilitate persistence of the parasite while producing little clinical disease. The mechanisms that contribute to the immunologic hyporesponsiveness in these patients remain undefined. IL-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous IL-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-IL-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)- or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-gamma production by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-gamma production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered IL-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of IL-10 only in infected subjects. PPD relative to SWAP induced fivefold less IL-10 release by CD4+ cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-IL-10 completely inhibited the parasite Ag-induced down-regulation of B7 expression. These studies indicate that IL-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.
King
C L
CL
Division of Geographic Medicine, Western Reserve University, Cleveland, OH 44106, USA.
Medhat
A
A
Malhotra
I
I
Nafeh
M
M
Helmy
A
A
Khaudary
J
J
Ibrahim
S
S
El-Sherbiny
M
M
Zaky
S
S
Stupi
R J
RJ
Brustoski
K
K
Shehata
M
M
Shata
M T
MT
D000293:Adolescent; D000328:Adult; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001483:Base Sequence; D002648:Child; D002908:Chronic Disease; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D012548:Schistosoma haematobium / Q000276:immunology*; D012553:Schistosomiasis haematobia / Q000276:immunology*
D000947:Antigens, Helminth; D017931:DNA Primers; D016753:Interleukin-10; D007371:Interferon-gamma