Marcelo B. Sztein

Generation of heterogeneous memory T cells by live attenuated tularemia vaccine in humans

There is very limited evidence concerning the phenotype, function, and homing characteristics of memory T (T(M)) cells elicited by vaccination against intracellular bacteria in humans. Here we studied T(M) subsets elicited by exposure to Francisella tularensis in humans as a model of immunity to intracellular bacteria. To this end, T(M) cells were evaluated in two groups: (1) subjects immunized with live attenuated tularemia vaccine by skin scarification and (2) tularemia naturally infected subjects. In both groups the immune responses were mediated by CD4(+) and CD8(+) effector T(M) cells, mostly CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-). Based on the expression of CD27, integrins alpha(4)/beta(7,) and alpha(4)/beta(1), it is likely that some of these T(M) cells have lytic potential and the ability to enter both mucosal and non-mucosal sites. Thus, regardless of whether by immunization or natural exposure, tularemia antigens elicited a broad spectrum of specific T(M) subsets with diverse homing characteristics.

Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium

Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4–8u2009years, are protected from malaria compared to matched schistosomiasis-negative (SN) children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4–14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6u2009months later, following cessation of malaria transmission. CD4+ T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17A) responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children (Pu2009<u20090.0001). At the time of malaria infection, 12/24 SN children and 15/23 SP children (Pu2009=u20090.29) stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children (Pu2009=u20090.009) at the convalescent timepoint. 46.2% of cytokine-producing CD4+ T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2–59.5%) of responses derived from CD45RA−CD62L− effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.