Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation

McKinstry, K. Kai; Alam, Fahmida; Flores-Malavet, Valeria; Nagy, Mate Z.; Sell, Stewart; Cooper, Andrea M.; Swain, Susan L.; Strutt, Tara M.

doi:10.1371/journal.ppat.1007989

Cited by 36 publications

(48 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are surprising as we, and others, have previously shown that this regime of S4B6 IL-2C administration drives dramatic increases in CD8 T cells and NK cells in the spleen, with smaller increases in CD4 and γδ T cells, and a modest increase in total B cells 14 . To determine whether the decrease in PP B cells required CD122-targeted IL-2 signals we next treated mice for 3 days with either PBS alone or with IL-2C made using the JES6-1 antibody clone, which targets IL-2 to CD25-expressing cells.…”

Section: Resultscontrasting

confidence: 76%

“…As part of our previous studies, we delivered S4B6 IL-2C systemically and investigated its impacts on immune cells in the spleen and lungs. We found, overall, that the general patterns observed in the spleen following S4B6 IL-2C administration were also seen in the lung, with increases in numbers of T cells and especially NK cells 14 . These results indicated that the regulation by IL-2 of major populations of immune cells present in secondary lymphoid organs and at mucosal sites is similar.…”

Section: Discussionmentioning

confidence: 55%

“…We investigated the impacts of these IL-2 signals on the cellular composition of GALT and compared them to changes observed in the spleen and peripheral lymph nodes in the same animals. IL-2C-induced changes in systemic secondary lymphoid organs are well documented in the literature, including by our own studies 14 , and thus analyses of these tissues provides an internal control within individual mice to verify the efficacy of IL-2C treatment.…”

Section: Resultsmentioning

confidence: 61%

See 2 more Smart Citations

CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer’s Patches

Singh

Dhume

Tejero

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Interleukin-2 (IL-2) has both pro- and anti-inflammatory properties that have been harnessed clinically and that are used experimentally to modulate leukocyte subsets in vivo. In mice, the bioavailability and half-life of IL-2 in vivo can be increased by complexing recombinant IL-2 with different clones of anti-IL-2 monoclonal antibodies that differentially target the cytokine to cells expressing different kinds of IL-2 receptors. While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration are well-defined in the spleen and peripheral lymph nodes, how immune cells in the gut and gut-associated lymphoid tissues respond to IL-2C is not well characterized. Here, we analyze how major leukocyte populations in these tissues respond to IL-2C. We find that IL-2C targeting cells expressing IL-2 receptor beta cause an acute decrease in cellularity of Peyer’s Patches while cell numbers in the lamina propria and intraepithelial lymphocytes are unaffected. Cell contraction in Peyer’s Patches is associated with the apoptosis of multiple B cell subsets. Our results are important to consider for understanding off-target impacts of IL-2C regimes in experimental models and for considering how IL-2 may contribute to the etiology or severity of gut-associated conditions such as Crohn’s Disease.

show abstract

Section: Resultscontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 61%

See 1 more Smart Citation

CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer’s Patches

Singh

Dhume

Tejero

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…IL-2 signals sustain the expression of STAT5 and Bcl-6, and promote expression of IL-7 receptor, thereby enabling the survival and maturation of CD4 + memory T cells [48,66]. Interestingly, however, IL-2-deficient memory CD4 + T cells generate a more vigorous and effective recall response against influenza virus than wild-type memory cells that produce IL-2 [67], suggesting that IL-2 and Bcl-6 may have regulatory or inhibitory roles once Ag-specific T cell memory has established, perhaps to prevent immunopathology during chronic antigen exposure. Of note, IL-2, IL-7, and IL-15, also known as common-gamma chain receptor cytokines, play key roles in memory (as well as in naïve and effector) CD4 + and CD8 + T cell development, homeostasis, and maintenance [68][69][70].…”

Section: T-bet the Master-regulator Of Th1 Cells Acts In An Expressmentioning

confidence: 99%

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Raphael

Joern

Forsthuber

2020

Cells

121

View full text Add to dashboard Cite

CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 + T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 + tissue-resident memory T cells and of CD4 + memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 + T cell-mediated autoimmune diseases.

show abstract

“…Natural Killer (NK) cells are a key component of the innate immune system and are critical in the response to many viral infections in humans and animal models (1)(2)(3). In addition to their beneficial antiviral role, NK cells have also been associated with immunopathology in infections such as respiratory syncytial virus (RSV) (4), influenza A virus (5)(6)(7)(8), and hepatitis B (9). Additionally, in the context of non-respiratory viral infections by HIV and HCV, NK cells appear to act as a rheostat by eliminating activated CD4+ and CD8+ T cells, thus preventing T cell-mediated autoimmunity (10).…”

Section: Introductionmentioning

confidence: 99%

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

et al. 2020

View full text Add to dashboard Cite

Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses.

show abstract

Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation

Cited by 36 publications

References 78 publications

CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer’s Patches

CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer’s Patches

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

Contact Info

Product

Resources

About