Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis.
In experimental Leishmania donovani infection in BALB/c mice, initial susceptibility gives way to T-cell-dependent acquired resistance and eventual control over visceral infection. Since various cytokines appear to underlie the host response to Leishmania infection, we examined infected liver tissue for gene expression of cytokines associated with Th1 (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]) and Th2 cells (IL-4 and IL-10). By Northern (RNA) blot analysis, only IFN-gamma mRNA expression was detected in livers of infected euthymic mice. To determine whether activation of Th1 cells develops selectively in this model, qualitative PCR analysis was used. These results indicated that mRNAs for IFN-gamma, IL-2, IL-4, and IL-10 were all induced by L. donovani infection. The potentially negative Th2 cell-associated response did not appear to play a functional role, however, since resistance was acquired, anti-IL-4 monoclonal antibody treatment did not accelerate control over visceral infection, and serum immunoglobulin E levels remained low. As judged by PCR analysis, IL-4 and IL-10 mRNAs were also expressed under three other conditions without apparent effect: in naive euthymic mice treated with IL-2, which induces leishmanicidal activity; in rechallenged immune mice, which resist reinfection; and in nude mice, which fail to control L. donovani. These results suggest that, like other Leishmania species, L. donovani infection may trigger a potentially suppressive Th2 cell-associated cytokine response. However, in T-cell-intact mice able to control L. donovani, this response either is insufficient to influence outcome or more likely is overshadowed by the Th1 cell response.
Miralles
G D
GD
Division of Infectious Diseases, Cornell University Medical College, New York, New York.
Stoeckle
M Y
MY
McDermott
D F
DF
Finkelman
F D
FD
Murray
H W
HW
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000502:physiology; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D015847:Interleukin-4