CD8⁺T Cells Have an Essential Role in Pulmonary Clearance of NontypeableHaemophilus influenzaefollowing Mucosal Immunization

Abstract

In the area of pulmonary bacterial infection it is still unclear which cells mediate the rapid upregulation and control of the inflammatory response which results in the resolution of infection and the minimization of local tissue damage (7,19,47). Classical innate immune responses involving macrophages and polymorphonuclear leukocytes (PMNs) have been seen to assist both immune and nonimmune animals in clearing infections from the lung over time. However, the cellular influx in immune animals is far greater and more rapid than in nonimmune controls (18,19). This rapid cellular response in the immune animals also corresponds to enhanced bacterial clearance and the more rapid resolution of inflammation, thus decreasing the opportunity for continued damage to local tissue. Alveolar macrophages, PMNs, and ␥␦ ϩ T cells have all demonstrated surveillance and phagocytic roles at mucosal surfaces (4, 40). Major histocompatibility complex class II (MHC-II)-restricted CD4 ϩ T cells have been associated with clearance of bacterial infection (14), whereas MHC-I-restricted CD8 ϩ T cells appear to be more involved with the clearance of infections, producing endogenous protein products such as in viral infections (11) or occasionally, for intracellular bacteria such as Listeria monocytogenes, via the MHC-I alternative pathway (37,38).The establishment of a mucosal immunization model looking at the kinetics of clearance of nontypeable Haemophilus influenzae (NTHI) in both immune and nonimmune rats and mice has enabled us to study the humoral and cellular interactions critical for enhanced clearance of bacteria from the lungs (18,19). Comparison of the rat and mouse models demonstrated that the kinetics of cellular infiltration, inflammatory cytokine production, and bacterial clearance follow similar patterns. Whereas antibody and PMNs appeared to be important factors utilized by previously immunized animals in clearing NTHI from the lungs during the latter phases of infection, prepriming of the immune system to clear the bacteria from the lung is controlled by mechanisms set in place at a very early time point post-NTHI challenge.To further investigate early control mechanisms in pulmonary bacterial clearance, the kinetics of recruitment of various lymphocyte subsets (including CD4 ϩ , CD8 ϩ , and ␥␦ ϩ T cells) and the levels of MHC-II marker expression were investigated in immune and nonimmune rats following challenge with NTHI. The observation that CD8 ϩ T cells were rapidly recruited to the lung in immunized animals following bacterial challenge led the investigators to deplete this cell type in mice. The mouse and rat models have been found to provide a similar response to NTHI following pulmonary challenge in both immunized and nonimmune animals. The combined data of rapid CD8 ϩ T-cell recruitment and enhanced bacterial clearance in animals with their full complement of CD8 ϩ T cells confirmed the role of these cells as a key cellular component in the upregulation of bacterial clearance from immunized animals.

Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced byHaemophilus influenzae

“…A comparable finding was observed in the present study, with the increase in CD4 + T-cells and decrease in CD19 + Bcells being observed in CNTHi-inoculated mice in particular. Foxwell et al [36] reported that CD8 + Tcells play an essential role in pulmonary clearance in rats after NTHi infection. Our present study supports the proposal that the potential role of CD8 + T-cells in the acute infectious stage may correlate with clearance of pathogens.…”

Classical and γδ T cells are each independently sufficient to establish protection against a classical strain of Klebsiella pneumoniae

“…These results indicate that T cells are required for the establishment and/or execution of protection against cKp challenge. Multiple T cell subsets have been demonstrated to mediate protective adaptive immune responses against bacteria in the lung including γδ ( Misiak et al., 2017 ), CD4 ( Wilk et al., 2017 ; Amezcua Vesely et al., 2019 ), and CD8 ( Foxwell et al., 2001 ) T cells. We identified increased populations of total gamma delta (editor, please convert to greek letters) T cells and total CD4 T cells, as well as increased populations of CD4+CD69+ and CD8+CD69+ T cells in the lung following cKp inoculation.…”

Leukocyte Infiltration of the Periarterial Space of the Lung after Allergen Provocation in a Rat Asthma Model

“…Intratracheal injection of ovalbumin-pulsed dendritic cells followed by exposure to ovalbumin aerosol also resulted in an accumulation of mononuclear cells in the periarterial space [22] . Exposure to different bacteria led to periarterial infi ltrations, too [23,24] . However, all these authors did not use electron microscopy and partly mentioned this phenomenon only incidentally.…”