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Marina A Kapina, Galina S Shepelkova, Vladimir V Mischenko, Peter Sayles, Polina Bogacheva, Gary Winslow, Alexander S Apt, Irina V Lyadova, CD27low CD4 T Lymphocytes That Accumulate in the Mouse Lungs during Mycobacterial Infection Differentiate from CD27high Precursors In Situ, Produce IFN-γ, and Protect the Host against Tuberculosis Infection, The Journal of Immunology, Volume 178, Issue 2, January 2007, Pages 976–985, https://doi.org/10.4049/jimmunol.178.2.976
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Abstract
The generation of effector, IFN-γ producing T lymphocytes and their accumulation at sites of infection are critical for host protection against various infectious diseases. The activation and differentiation of naive T lymphocytes into effector memory cells starts in lymphoid tissues, but it is not clear whether the Ag-experienced cells that leave lymph nodes (LN) are mature or if they undergo further changes in the periphery. We have previously shown that CD44highCD62Llow effector CD4 T lymphocytes generated during the course of mycobacterial infection can be segregated into two subsets on the basis of CD27 receptor expression. Only the CD27low subset exhibited a high capacity for IFN-γ secretion, indicating that low CD27 expression is characteristic of fully differentiated effector CD4 T lymphocytes. We demonstrate now that CD27low IFN-γ-producing CD4 T lymphocytes accumulate in the lungs but are rare in LNs. Several factors contribute to their preferential accumulation. First, CD27low CD4 T lymphocytes present in the LN are highly susceptible to apoptosis. Second, circulating CD27low CD4 T cells do not enter the LN but efficiently migrate to the lungs. Third, CD27high effector CD4 T cells that enter the lungs down-regulate CD27 expression in situ. In genetically heterogeneous mice that exhibit varying susceptibility to tuberculosis, the accumulation of mature CD27low CD4 T cells in the lungs correlates with the degree of protection against infection. Thus, we propose that terminal maturation of effector CD4 T lymphocytes in the periphery provides the host with efficient local defense and avoids potentially harmful actions of inflammatory cytokines in lymphoid organs.
