EXPRESSION OF IL-10R ON LYMPH NODES AND SPLEEN CELLS OF BORRELIA-INFECTED MICE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We previously reported that the proinflammatory cytokines interferon-gamma (IFN-?) and interleukin-6 (IL-6), produced in response to lipidated outer surface protein A (L-OspA) and the synthetic lipohexapeptide Pam3Cys, were more efficiently inhibited by the anti-inflammatory cytokine IL-10 in lymph node (LN) cells of disease-resistant C57BL/6J than in those of disease-susceptible C3H/HeJ mice. The ability of IL-10 to efficiently down-modulate these cytokines in LN cells of C57 mice as compared with those of C3H mice correlated with the expression of significantly more IL-10 receptor (IL-10R)-bearing cells in LN of C57 than in those of C3H mice. On the contrary, spleen cells from both strains of mice showed similar levels of IL-10R bearing cells, correlating with the ability of IL-10 to dampen the production of IFN-? and IL-6 with the same efficiency in spleen cell cultures of both strains of mice. In this study, we investigated the specific lymphocyte population in LN cells that may be the target of IL-10 inhibition of proinflammatory cytokines in mice. LN and spleen cells were obtained ex vivo after one-week of infection of C3H and C57 mice with B. burgdorferi and assessed for IL-10R expression on CD3+ CD4+, CD8+ and CD19+ lymphocytes by flow cytometry. The majority of IL-10R bearing cells were of the CD19+ phenotype (B cells) in LN and spleen cells from C3H and C57 mice. However, CD19+ cells from C3H mice expressed more IL-10R than those of C57 mice, suggesting that CD19+ cells are most likely not the targets of IL-10 down-modulation of proinflammatory cytokines, given the greater efficiency by which IL-10 inhibits proinflammatory cytokines in LN cells of C57 mice. Neither CD3+, CD4+ nor CD8+ T lymphocytes expressed a significant percentage of IL-10R. These findings may suggest that other IL-10R bearing cells such as macrophages or dendritic cells may be targets of IL-10 inhibition of inflammatory cytokines in the LN and spleen of mice with Lyme disease.