Cutting Edge: Control of Mycobacterium tuberculosis Infection by a Subset of Lung Parenchyma–Homing CD4 T Cells

Abstract

Th1 cells are critical for containment of Mycobacterium tuberculosis infection, but little else is known about the properties of protective CD4 T cell responses. In this study, we show that the pulmonary Th1 response against M. tuberculosis is composed of two populations that are either CXCR3hi and localize to lung parenchyma or are CX3CR1hiKLRG1hi and are retained within lung blood vasculature. M. tuberculosis–specific parenchymal CD4 T cells migrate rapidly back into the lung parenchyma upon adoptive transfer, whereas the intravascular effectors produce the highest levels of IFN-γ in vivo. Importantly, parenchymal T cells displayed greater control of infection compared with the intravascular counterparts upon transfer into susceptible T cell–deficient hosts. Thus, we identified a subset of naturally generated M. tuberculosis–specific CD4 T cells with enhanced protective capacity and showed that control of M. tuberculosis correlates with the ability of CD4 T cells to efficiently enter the lung parenchyma rather than produce high levels of IFN-γ.

Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

“…In addition, we observed only minimal expression of CXCR3 and CCR5, on both CD103 + and CD103 2 IFN-g + CD8 + T cell subsets. These findings differ from recent observations in M. tuberculosis-infected mice, which show high expression of CXCR3 on lung T RM cells (16). More study of chemokine receptors on influenza-specific lung T RM cells is required to elucidate to importance of chemokine receptors in establishing tissue residence.…”

“…5E). As PD-1, a cell surface marker of activated T cells is known to express on T RM cells (16,35), we showed that high expression of PD-1 was consistently detected on lung CD103 + compared with CD103 2 IFN-g + CD8 + T cells. In addition, the expression levels of chemokine receptors involved in T cell migration into the lung (36, 37), CXCR3 and CCR5, were minimal with no significant difference between either subset (Fig.…”

“…It has been suggested that the ability of memory T cells to home to the lung parenchyma as T RM is critical to control lung pathogens such as influenza and Mycobacterium tuberculosis (15,16 (53). In this study, we did not compare the kinetics of cytokine production between lung CD103 + CD8…”

“…These long-lived nonrecirculating T RM cells permanently reside in nonlymphoid tissues including skin, brain, vagina, and lung and provide rapid, effective local protection against reinfection relative to circulating counterpart memory T cells (10,11). Local immune protection by T RM cells has been consistently documented in murine models of virus and bacterial infections including vaccinia virus, lymphocytic choriomeningitis virus, HSV, influenza, and tuberculosis (12)(13)(14)(15)(16). Recent studies have revealed delivery of vaccinia virus in mice via skin scarification generates long-lived skin T RM CD8 + T cells associated with improved long-term immunity (12,17).…”

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

“…The availability of the recently developed technique of intravascular staining helps to discriminate pulmonary intravascular and lung tissue T-cell populations for the first time [16,17], and appreciate their relationship with anti-TB protection. In our previous studies we have reported that, regardless of route of immunisation, a large population of anti-TB T-cells can be isolated from perfused mouse lungs [12,13].…”