CD27low CD4 T lymphocytes that accumulate in the mouse lungs during mycobacterial infection differentiate from CD27high precursors in situ, produce IFN-gamma, and protect the host against tuberculosis infection.
The generation of effector, IFN-gamma 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 CD44(high)CD62L(low) 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 CD27(low) subset exhibited a high capacity for IFN-gamma secretion, indicating that low CD27 expression is characteristic of fully differentiated effector CD4 T lymphocytes. We demonstrate now that CD27(low) IFN-gamma-producing CD4 T lymphocytes accumulate in the lungs but are rare in LNs. Several factors contribute to their preferential accumulation. First, CD27(low) CD4 T lymphocytes present in the LN are highly susceptible to apoptosis. Second, circulating CD27(low) CD4 T cells do not enter the LN but efficiently migrate to the lungs. Third, CD27(high) 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 CD27(low) 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.
Kapina
Marina A
MA
Department of Immunology, Central Institute for Tuberculosis of the Russian Academy of Medical Sciences, Moscow, Russia.
Shepelkova
Galina S
GS
Mischenko
Vladimir V
VV
Sayles
Peter
P
Bogacheva
Polina
P
Winslow
Gary
G
Apt
Alexander S
AS
Lyadova
Irina V
IV
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma