Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens.
Mycobacterium tuberculosis infects one-third of the global population and claims two million lives every year. Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children. Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts. Ex vivo analysis of the expression of CD45RA and CCR7 surface markers indicated a skewed representation of Ag85A epitope-specific CD8 T cells during active TB, with a predominance of T central memory cells and a decrease of terminally differentiated T cells, which was reversed after therapy. Accordingly, pentamer-specific CD8 T cells from tuberculous patients produced low levels of IFN-gamma and had low expression of perforin, which recovered after therapy. The finding of an elevated frequency of pentamer-specific CD8 T cells with T effector memory and terminally differentiated phenotypes in the cerebrospinal fluid of a child with tuberculous meningitis strongly indicates compartmentalization of such CD8 effectors at the site of disease. Our study represents the first characterization of Ag-specific memory and effector CD8 T cells during TB and may help to understand the type of immune response that vaccine candidates should stimulate to achieve protection.
Caccamo
Nadia
N
Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
Meraviglia
Serena
S
La Mendola
Carmela
C
Guggino
Giuliana
G
Dieli
Francesco
F
Salerno
Alfredo
A
D000942:Antigens, Bacterial / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D018984:Epitopes, T-Lymphocyte / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000097:blood; D015789:HLA-A2 Antigen; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology; D014373:Tuberculin / Q000096:biosynthesis; D014390:Tuberculosis, Meningeal / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014373:Tuberculin; C065036:antigen 85, Mycobacterium bovis; D054353:Perforin; D007371:Interferon-gamma