CD4+ T cell subsets in experimental cutaneous leishmaniasis

Virulent Toxoplasma gondii strain RH promotes T-cell-independent overproduction of proinflammatory cytokines IL12 and γ-interferon

“…In addition, the highly susceptible C57BL/6 mice die from peroral infection with strain ME49, developing severe necrosis of the small intestine and the liver with overproduction of IL12 and IFN-ª. When mice were treated with anti-IFN-ª or anti-IL12 antibodies, the development of the small intestine and liver necrosis was prevented and the time before death was prolonged (Scott et al, 1988;Liesenfeld et al, 1997;Suzuki et al, 2000). Finally, Mordue et al (2001) reported similar findings of acute toxoplasmosis leading to lethal overproduction of Th1 cytokines, including IL12, IL18 and IFN-ª, by using the virulent strain RH and a different T. gondii strain (PTG), which is of lower virulence.…”

“…Absence of any one of these proinflammatory mediators results in increased mortality during infection as a result of uncontrolled tachyzoite growth (Gazzinelli et al, 1994;Sher et al, 1993). Similarly, in Leishmania infection, a Th1 response, characterized by the production of proinflammatory cytokines, is protective, whereas a Th2 response with secretion of anti-inflammatory cytokines is pathogenic (Scott et al, 1988;Scott, 1991).…”

Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease‐promoting CD4+ cells are different from TH2 cells

“…In the present LD studies, it is notable that IL2 production by CD4+ cells from susceptible mice was never paired with significant secretion of IFN-y. Thus, these CD4+ cells do not represent typical T H~ cells which have originally been classified on the basis of studies with long-term cultured Tcell clones.The development of CD4+ cells into T H~ or T H~ cells, or intermediates thereof, may depend on the strain of mice infected with L. major, the composition of the antigen [15,34], or the type of APC.The LD system used here for studying the T cell response to whole L. major promastigotes is well suited to test these possibilities.…”

“…The ability to contain lesion development and complete healing can be induced by various treatments of BALBk mice prior to infection, e.g. sublethal irradiation [l], injection of anti-IgM [2], or anti-CD4 [3] Ab, or immunization with purified parasite Ag [4][5][6].The events leading to resistance are thought to be initiated by lymphokines with MQ-activating properties, predominantly IFN-y, that are generated by L. majoractivated T cells . Evidence points to the CD4+ population as being the critical source of resistancepromoting Tcells [lo-121.…”

Cytokines in the differentiation of Th1/Th2 CD4+ subsets in leishmaniasis

“…Earlier studies in the L. major system demonstrated that distinct antigens could induce the selective maturation of distinct T helper subsets [12,15,161, suggesting that different precursor T cells might explain the polarized immune response in this disease. However, more recent TCR types, whereas responses to distinct antigens would be predicted to have diverse TCR types.…”