CD4 T cells producing IFN-gamma in the lungs of mice challenged with mycobacteria express a CD27-negative phenotype.
Protection against tuberculosis depends upon the generation of CD4(+) T cell effectors capable of producing IFN-gamma and stimulating macrophage antimycobacterial function. Effector CD4(+) T cells are known to express CD44(hi)CD62L(lo) surface phenotype. In this paper we demonstrate that a population of CD44(hi)CD62L(lo) CD4(+) effectors generated in response to Mycobacterium bovis BCG or M. tuberculosis infection in C57BL/6 mice is heterogeneous and consists of CD27(hi) and CD27(lo) T cell subsets. These subsets exhibit a similar degree of in vivo proliferation, but differ by the capacity for IFN-gamma production. Ex vivo isolated CD27(lo) T cells express higher amounts of IFN-gamma RNA and contain higher frequencies of IFN-gamma producers compared to CD27(hi) subset, as shown by real-time PCR, intracellular staining for IFN-gamma and ELISPOT assays. In addition, CD27(lo) CD4(+) T cells uniformly express CD44(hi)CD62L(lo) phenotype. We propose that CD27(lo) CD44(hi)CD62L(lo) CD4(+) T cells represent highly differentiated effector cells with a high capacity for IFN-gamma secretion and antimycobacterial protection at the site of infection.
Lyadova
I V
IV
Trudeau Institute, Inc., Saranac Lake, New York, USA. ivlyadova@mail.ru
Oberdorf
S
S
Kapina
M A
MA
Apt
A S
AS
Swain
S L
SL
Sayles
P C
PC
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D010641:Phenotype; D012333:RNA, Messenger; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D001500:BCG Vaccine; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019041:L-Selectin; D007371:Interferon-gamma