B cells modulate T cells so as to favour T helper type 1 and CD8+ T-cell responses in the acute phase of Trypanosoma cruzi infection.
In this study, we have evaluated the production of pro- and anti-inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (mu MT KO). The results show that Trypanosoma cruzi infection in C57Bl/6m mu MT KO mice is intensified in relation to control mice and this exacerbation is related to low levels of inflammatory cytokines produced during the acute infection and the lower numbers of central and effector memory CD4(+) and CD8(+) T cells generated during the acute phase of the infection. In addition, a marked reduction in the CD8(+) T-cell subpopulation was observed in mu MT KO infected mice. In agreement to this, the degree of tissue parasitism was increased in mu MT mice and the tissue inflammatory response was much less intense in the acute phase of the infection, consistent with a deficit in the generation of effector T cells. Flow cytometry analysis of the skeletal muscle inflammatory infiltrate showed a predominance of CD8(+) CD45Rb low in B-cell-sufficient C57Bl/6 mice, whereas the preponderant cell type in mu MT KO skeletal muscle inflammatory infiltrate was CD4(+) T cells. In addition, CD8(+) T cells found in skeletal muscle from mu MT KO infected mice were less activated than in control B-cell sufficient infected mice. These results suggest that B cells may participate in the generation of effector/memory T cells. In addition and more importantly, B cells were crucial in the maintenance of central and effector memory CD8(+) T cell, as well as the determination of the T cell cytokine functional pattern, and they may therefore account for critical aspects of the resistance to intracellular pathogens, such as T. cruzi.
Cardillo
Fabiola
F
Cellular Immunology, Autoimmunity and Experimental Chagas Disease Laboratory, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, Salvador, Bahia, Brazil.
Postol
Edilberto
E
Nihei
Jorge
J
Aroeira
Luiz S
LS
Nomizo
Auro
A
Mengel
José
J
D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004198:Disease Susceptibility; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018512:Parasitemia / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D007378:Interleukins; D007371:Interferon-gamma