In:
The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 2 ( 2007-01-15), p. 976-985
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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.178.2.976
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2007
detail.hit.zdb_id:
1475085-5
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