Granulysin-expressing CD4+ T cells as candidate immune marker for tuberculosis during childhood and adolescence.
BACKGROUND
Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB.


METHODS
Peripheral blood mononuclear cells (PBMC) from children and adolescents (1-17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4(+) CD45RO(+) memory T cells.


RESULTS
CD4(+) CD45RO(+) T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSE(low)CD4(+)CD45RO(+)) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4(+) T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells.


CONCLUSIONS
Our data suggest granulysin expression by CD4(+) memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence.
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Henrik
H
Mueller
Kellen C
KC
Faé
Klaus
K
Magdorf
Christian A
CA
Ganoza
Ulrich
U
Wahn
Ute
U
Guhlich
Cornelia
C
Feiterna-Sperling
Stefan H E
SH
Kaufmann
D000293:Adolescent; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D014376:Tuberculosis / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; C075005:GNLY protein, human