CELLULAR MEDIATORS OF ANTI-LISTERIA IMMUNITY AS AN ENLARGED POPULATION OF SHORT-LIVED, REPLICATING T CELLS

Abstract

An intravenous immunizing infection with the facultative, intracellular parasite, Listeria monocytogenes results in the production in the spleen of a population of immunologically-committed lymphocytes which can adoptively immunize normal recipients against a lethal challenge infection. These cellular mediators of immunity are first produced in the spleen between days 2 and 4 of infection and reach peak production on day 6. Their production then progressively decreases until about day 20 when their presence can no longer be detected. Increased production of cellular mediators is coincident with major increases in cell division, cellularity, and spleen weight. Decreased production of cellular mediators, on the other hand, is associated with decreases in cell division, cellularity, and spleen weight. Again, the level of delayed sensitivity to Listeria antigens expressed by the host at any one time is proportional to the number of cellular mediators in the spleen. Increased production of cellular mediators is also associated with major increases in the total numbers of replicating T cells and B cells in the spleen. That the cellular mediators of immunity are part of the replicating T cell population, rather than the B cell population, is evidenced by their susceptibility to anti-θ serum and by their resistance to anti-Ig serum. Furthermore, they can be completely eliminated from the spleen by a brief pulse of the antimitotic drug, vinblastine. This study allows the conclusion that the cellular mediators of anti-Listeria immunity belong to an expanded population of rapidly dividing, short-lived T cells. It is suggested that they have the same properties as the T cell effectors of allograft immunity.

The Onset of CD8+-T-Cell Contraction Is Influenced by the Peak ofListeria monocytogenesInfection and Antigen Display

“…In the context of ⌬actA L. monocytogenes infection, the magnitude of infection and the length of Ag display had little effect upon the timing of CD8 ϩ -T-cell contraction (4). However, in virulent L. monocytogenes infection, the infection was prolonged and the peak of the CD8 ϩ -T-cell response was delayed compared to reports of attenuated L. monocytogenes infection (4,10,14,16,29,34,52). One potential explanation for this discrepancy was that the timing of the peak of infection had more influence upon the onset of T-cell contraction than the total length of Ag display.…”

“…One difference between virulent and ⌬actA L. monocytogenes infections is the time course of infection (14,16,29,34,52). Thus, we hypothesized that these differences in infection kinetics lead to differences in Ag presentation and the timing of CD8…”

Protection from Bacterial Infection by a Single Vaccination with Replication-Deficient Mutant Herpes Simplex Virus Type 1

“…Vaccines utilizing inactivated or recombinant bacteria have been demonstrated to elicit both CD4-and CD8-T-cell activation (16), but they seem to be inefficient stimulators of effector (25) and memory (34) T cells if compared side by side with live bacteria (25) or recombinant viral vaccines (34). In this respect, inactivated intracellular bacterial vaccines are similar to natural M. tuberculosis (44) and L. monocytogenes (33) infections, which fail to induce sufficient immunological memory to prevent recurrent infections. DNA vaccines have been demonstrated to induce protection against infections with M. tuberculosis (43) and L. monocytogenes (9).…”

Depletion of a γδ T Cell Subset Can Increase Host Resistance to a Bacterial Infection

“…Mice infected with Listeria mount an ␣␤ T cell-mediated adaptive immune response that is only first weakly detectable on the third day of infection (43). The detrimental effect of removing V␥1 ϩ cells during a Listeria infection at an early time point thus suggested that they primarily influence components of the innate immune response.…”