Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors

Khanna, Ashwani; Plummer, Matthew; Nilakantan, Vani; Pieper, Galen M.

doi:10.4049/jimmunol.174.12.7610

Cited by 15 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although previous studies showed that p21 has a role in various T cell proliferation systems, the conditions that render T cell proliferation p21 dependent remained undefined (4,8,14,28,29). In this study, we explored the role of p21 in T cell proliferation of activated/memory T cells and reached the following conclusions: 1) p21 does not affect naive T cell proliferation, but exerts its control on activated/memory T cells; 2) p21 does not affect AICD, but regulates proliferation of memory T cells that survive AICD; 3) p21 regulates responses of in vivo generated memory T cells; and 4) p21 deficiency increases CD4…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

p21CIP1/WAF1 Controls Proliferation of Activated/Memory T Cells and Affects Homeostasis and Memory T Cell Responses

Arias

Ballesteros-Tato

García

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Development of autoantibodies and lupus-like autoimmunity by 129/Sv × C57BL/6 p21−/− mice has established that cell cycle deregulation is one the defective pathways leading to break of tolerance. Memory T cell accumulation is thought to be related to tolerance loss in murine lupus models. We studied T cell memory responses in C57BL/6 p21−/− mice that develop lupus-like disease manifestations. p21 did not affect primary proliferation of naive T cells, and was required for cycling control, but not for apoptosis of activated/memory T cells. When we induced apoptosis by secondary TCR challenge, surviving memory T cells depended on p21 for proliferation control. Under conditions of secondary T cell stimulation that did not cause apoptosis, p21 was also needed for regulation of activated/memory T cell expansion. The requirement for p21 in the control of T cell proliferation of activated/memory T cells suggests that in addition to apoptosis, cycling regulation by p21 constitutes a new pathway for T cell homeostasis. Concurring with this view, we found accumulation in p21−/− mice of memory CD4+ T cells that showed increased proliferative potential after TCR stimulation. Furthermore, OVA immunization of p21−/− mice generated hyperresponsive OVA-specific T cells. Overall, the data show that p21 controls the proliferation of only activated/memory T cells, and suggest that p21 forms part of the memory T cell homeostasis mechanism, contributing to maintenance of tolerance.

show abstract

Section: Discussionmentioning

confidence: 99%

“…These findings suggest that p21 control of cycling may depend on T cell activation status. Other studies showed inhibition of T cell proliferation after transfection with p21 (28) or direct uptake of recombinant p21 protein (29), although T cell status is not discussed.…”

mentioning

confidence: 99%

p21CIP1/WAF1 Controls Proliferation of Activated/Memory T Cells and Affects Homeostasis and Memory T Cell Responses

Arias

Ballesteros-Tato

García

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Proliferation of splenocytes is a widely used marker of the immune activation [30,31]. The effect of DIM concentrations ranging from 1 to 20 μM on proliferation of splenocytes was therefore examined using a [ 3 H]thymidine incorporation assay.…”

Section: Dim Induces and Augments Splenocyte Proliferationmentioning

confidence: 99%

3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo

Xue

Pestka

et al. 2008

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

3,3'-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol, exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-gamma) production and potentiates the IFN-gamma signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-gamma receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the effects of DIM were evaluated in a panel of murine immune function tests that included splenocyte proliferation, reactive oxygen species (ROS) generation, cytokine production and resistance to viral infection. DIM was found to induce proliferation of splenocytes as well as augment mitogen- and interleukin (IL)-2-induced splenocyte proliferation. DIM also stimulated the production of ROS by murine peritoneal macrophage cultures. Oral administration of DIM, but not intraperitoneal injection, induced elevation of serum cytokines in mice, including IL-6, granulocyte colony-stimulating factor (G-CSF), IL-12 and IFN-gamma. Finally, in a model of enteric virus infection, oral DIM administration to mice enhanced both clearance of reovirus from the GI tract and the subsequent mucosal IgA response. Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole.

show abstract

“…However, T cells are known to be difficult to transfect with adenoviral vectors (45,46). It has also been reported that exogenous p21 protein is capable of entering T cells, localizing in the nucleus, and inhibiting proliferation and proinflammatory cytokine production in response to mitogenic stimulation (47). Thus another possible scenario is that exogenous p21 transgene product secreted by DC or other transfected cells of the spleen could influence T cell behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Manipulation of p21 may constitute such an approach. Indeed, the finding that recombinant p21 protein may inhibit T cell responses (47) points to the potential of this approach as a therapeutic modality and certainly warrants further investigation. …”

Section: Discussionmentioning

confidence: 99%

Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Welling

Csencsits

et al. 2008

Surgery

View full text Add to dashboard Cite

Background-The cyclin-dependent kinase (cdk) inhibitor p21 inhibits cellular proliferation of many cell types, including T cells. However, autoimmune models have yielded conflicting results regarding the role of cdk inhibitors and T cell function. The role of p21 in T cell function following transplantation has not been directly investigated. We hypothesized that p21 plays an important role in alloantigen-driven responses in vitro in mixed lymphocyte cultures (MLC) and in vivo using the heterotopic murine cardiac allograft model.

show abstract

Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors

Cited by 15 publications

References 43 publications

p21CIP1/WAF1 Controls Proliferation of Activated/Memory T Cells and Affects Homeostasis and Memory T Cell Responses

p21CIP1/WAF1 Controls Proliferation of Activated/Memory T Cells and Affects Homeostasis and Memory T Cell Responses

3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo

Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Contact Info

Product

Resources

About