Kinetics of ex-vivo cytokine production by splenocytes during murine acquired immunodeficiency syndrome (MAIDS).
The role of T helper 1 (Th1) and T helper 2 (Th2) responses in the murine acquired immunodeficiency syndrome (MAIDS) is unclear. It has been suggested that differential activation of T cell subsets, particularly a shift to Th2 cytokine production, may be associated with disease progression. To clarify the regulation of the cytokine network in the course of MAIDS, we examined the kinetics of cytokine production by isolated splenocytes. C57/BL6 mice were infected with the LP-BM5 mixture. The spleen cell proliferative response, together with IL-2, IFN-gamma, IL-10 and IL-4 production by unstimulated and ConA or anti-CD3 MoAb-stimulated spleen cells, were determined at various times after inoculation (weeks 1, 3, 6 and 9). Spleen cells isolated from murine leukemia virus complex (LP-BM5) infected mice spontaneously produced significant amounts of IL-2 and IFN-gamma one and three weeks post-infection, compared to uninfected controls. The capacity of isolated T cells to produce the Th1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and anti-CD3 MoAb decreased after 3 weeks of infection. The fall in IL-2 production ran parallel to the fall in the T cell proliferative response to ConA. IL-10 production in response to ConA and anti-CD3 MoAb increased after three weeks post-inoculation, and followed the reverse kinetic pattern to IFN-gamma and IL-2. In contrast, no significant spontaneous IL-4 production and no increase in IL-4 production in response to ConA or anti-CD3 MoAb occurred during the course of MAIDS, relative to uninfected controls. These results suggest that LP-BM5 infection leads to a fall in Th1 cytokine production rather than a clear switch to Th2 cytokine production.
Akarid
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INSERM U 13, Hôpital Bichat-Claude Bernard, Paris, France.
Pocidalo
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MA
Desforges
B
B
Sinet
M
M
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D016183:Murine Acquired Immunodeficiency Syndrome / Q000473:pathology*; D016853:Muromonab-CD3 / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D007376:Interleukin-2; D008934:Mitogens; D016853:Muromonab-CD3; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma