Recall of long-lived immunity to Mycobacterium tuberculosis infection in mice.
Our study investigates the recall of immunity in the mouse model of memory immunity to tuberculosis infection. The results provide evidence that recall of immunity is expressed as an accelerated accumulation of potent effector cells in the infected target organs. These effector cells were recruited from the resting pool of memory cells and were immediately triggered to exert their effector functions, leading to a massive release of Th1 cytokines detectable both in splenic extracts and in the serum within the first 24 h of infection. During a primary infection, in contrast, a 14-day delay was observed before significant cytokine levels were reached. After the initial effector phase, the cells blasted and entered into clonal expansion, resulting in a rapid increase in the total number of CD4 CD45RBlow cells in the spleen. The recall of memory immunity was highly efficient and controlled an infectious challenge within the first week. The molecules recognized by the memory effector subset were the proteins secreted from Mycobacterium tuberculosis during growth. By separating the CD4 population into CD45RBhigh and CD45RBlow subsets, the memory effector cells were demonstrated to reside predominantly in the activated population of CD45RBlow CD44high LFA-1high L-selectinlow cells. The key antigenic targets recognized by these cells were identified as Ag85B and a secreted 6-kDa protein (ESAT-6) that elicited the release of exceedingly high levels of IFN-gamma. ESAT-6 was biochemically purified, characterized, and the gene encoding the protein was cloned.
Andersen
P
P
Department of Bacterial Vaccine, Statens Seruminstitut, Copenhagen, Denmark.
Andersen
A B
AB
Sørensen
A L
AL
Nagai
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D015151:Immunoblotting; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines