Depletion of CD8+ T Cells Exacerbates CD4+ Th Cell-Associated Inflammatory Lesions During Murine Mycoplasma Respiratory Disease

Jones, Harlan P.; Tabor, Leslie; Sun, Xiangle; Woolard, Matthew D.; Simecka, Jerry W.

doi:10.4049/jimmunol.168.7.3493

Cited by 79 publications

(113 citation statements)

References 61 publications

(49 reference statements)

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“…When CD8 + T cells were depleted from mice prior to infection with M. pulmonis, disease severity increased (Jones et al, 2002). Similar results were observed in studies involving rats.…”

Section: Mycoplasmasupporting

confidence: 73%

“…Studies utilizing M. pulmonis have shown that disease severity is directly related to Th cells. Depletion of these cells prior to infection led to significant decreases in disease severity, as measured by weight loss and lesion incidence (Jones et al, 2002). Since Th cell responses can be separated into Th1 or Th2 lineages, further studies were performed using IFN--deficient mice and IL-4-deficient mice.…”

Section: Mycoplasmamentioning

confidence: 99%

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The Contrasting Roles of T Regulatory Cells in Bacterial Lung Diseases

Odeh¹,

Simecka²

2012

Respiratory Diseases

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“…When CD8 + T cells were depleted from mice prior to infection with M. pulmonis, disease severity increased (Jones et al, 2002). Similar results were observed in studies involving rats.…”

Section: Mycoplasmasupporting

confidence: 73%

Section: Mycoplasmamentioning

confidence: 99%

The Contrasting Roles of T Regulatory Cells in Bacterial Lung Diseases

Odeh¹,

Simecka²

2012

Respiratory Diseases

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“…CD8 ϩ T cells have been reported to act as negative regulators of inflammation in certain models of disease. For example, a regulatory role for CD8 ϩ T cells in controlling CD4 ϩ T cell-mediated inflammatory response has been described in a mouse model of Mycoplasma pulmonis respiratory disease (19). It is apparent that a similar phenomenon is occurring in our studies that merits further study.…”

Section: Discussionmentioning

confidence: 60%

“…We have demonstrated that CD8 ϩ T cells are required for maximal inflammation and lung injury, but have little effect on P. carinii clearance (39). It has also been demonstrated that CD8 ϩ T cells can suppress specific immune responses by helping to limit the intensity and duration of CD4 ϩ T cell responses (19). Therefore, understanding the interplay of CD4 ϩ and CD8 ϩ T cells during IRD, and how each subset contributes to clearance, injury, and/or control of inflammation, is necessary to develop optimal treatment regimens for PcP-related IRD.…”

mentioning

confidence: 98%

Contribution of T cell subsets to the pathophysiology ofPneumocystis-related immunorestitution disease

Bhagwat

Gigliotti²,

Xu³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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.-Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4 ϩ and CD8 ϩ T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4 ϩ cells were more abundant than CD8 ϩ cells during the acute stage of IRD that coincided with impaired pulmonary physiology and organism clearance. Conversely, CD8 ϩ cells were more abundant during the resolution phase following P. carinii clearance. Depletion of CD4 ϩ T cells protected mice from the acute pathophysiology of IRD. However, these mice could not clear the infection and developed severe PcP at later time points when a pathological CD8 ϩ T cell response was observed. In contrast, mice depleted of CD8 ϩ T cells efficiently cleared the infection but developed more severe disease, an increased frequency of IFN-␥-producing CD4 ϩ cells, and a prolonged CD4 ϩ T cell response than mice with both CD4 ϩ and CD8 ϩ cells. These data suggest that CD4 ϩ T cells mediate the acute respiratory disease associated with IRD. In contrast, CD8 ϩ T cells contributed to neither lung injury nor organism clearance when CD4 ϩ cells were present, but instead served to modulate CD4 function. In the absence of CD4 ϩ cells, CD8 ϩ T cells produced a nonprotective, pathological immune response. These data suggest that the interplay of CD4 ϩ and CD8 ϩ T cells affects the ultimate outcome of PcP-related IRD.inflammation; pulmonary physiology; acquired immune deficiency syndrome PNEUMOCYSTIS carinii IS an opportunistic fungus that causes pneumonia in immune-compromised patients (37), including patients with acquired immune deficiency syndrome (AIDS) (29), patients undergoing chemotherapy, and patients receiving treatment with immunosuppressive drugs during organ transplantation (34). Although exposure to P. carinii is nearly universal, as demonstrated by the appearance of anti-P. carinii antibody in 85% of children by the age of 20 mo (35), a period of immunosuppression is essential for the development of clinical disease (15,34). Several studies have demonstrated a positive correlation between the degree of inflammation and the severity of disease (4,23,36), suggesting that the pathogenesis of Pneumocystis pneumonia (PcP) is primarily inflammatory in nature, in that infection with P. carinii is necessary to cause pneumonia, but certain aspects of the immune response against P. carinii are responsible for the associated pathophysiology (30, 39). For example, AIDS patients who demonstrate a rapid recovery of CD4 ϩ T lymphocytes after institution of combined antiretroviral therapy may develop pulmonary decompensation in response to preexisting pulmonary infections, including P. carinii (26). This clinical syndrome has been termed "immunorestitution disease" (IRD) (9). At least one study that examined t...

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“…The depletion of Th cells results in less severe lung disease, demonstrating that a Th cell response contributes to disease pathology in the lung (16). To the contrary, depletion of CD8 ϩ T cells from mice leads to an exacerbation of mycoplasma pulmonary disease.…”

mentioning

confidence: 99%

The Upper and Lower Respiratory Tracts Differ in Their Requirement of IFN-γ and IL-4 in Controlling Respiratory Mycoplasma Infection and Disease

Woolard

Hodge

Jones

et al. 2004

The Journal of Immunology

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The purpose of this study is to evaluate the significance of IFN-γ and IL-4 production in controlling mycoplasma infection and the pathogenesis of disease in the upper and lower respiratory tract. By using IFN-γ knockout and IL-4 knockout BALB/c mice, we were able to study the contribution of these cytokines in the development of pathogenesis and/or protection in response to mycoplasma respiratory infection, in both the upper and lower respiratory tracts. The loss of either IFN-γ or IL-4 does not affect disease pathogenesis or mycoplasma organism numbers in the upper respiratory tract. However, in the absence of IL-4, the nasal passages developed a compensatory immune response, characterized by higher numbers of macrophages and CD8+ T cells, which may be masking detrimental effects due to IL-4 deficiency. This is in contrast to the lower respiratory tract, where the loss of IFN-γ, but not IL-4, leads to higher mycoplasma numbers and increased disease severity. The loss of IFN-γ impacted the innate immune system’s ability to effectively clear mycoplasma, as the number of organisms was higher by day 3 postinfection. This higher organism burden most likely impacted disease pathogenesis; however, the development of Th2 cell-mediated adaptive immune response most likely contributed to lesion severity at later time points during infection. Our studies demonstrate that the upper and lower respiratory tracts are separate and distinct in their cytokine requirements for generating immunity against mycoplasma infection.

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Depletion of CD8+ T Cells Exacerbates CD4+ Th Cell-Associated Inflammatory Lesions During Murine Mycoplasma Respiratory Disease

Cited by 79 publications

References 61 publications

The Contrasting Roles of T Regulatory Cells in Bacterial Lung Diseases

The Contrasting Roles of T Regulatory Cells in Bacterial Lung Diseases

Contribution of T cell subsets to the pathophysiology ofPneumocystis-related immunorestitution disease

The Upper and Lower Respiratory Tracts Differ in Their Requirement of IFN-γ and IL-4 in Controlling Respiratory Mycoplasma Infection and Disease

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