Effects of Interleukin-15 on<i>In Vitro</i>Human T Cell Proliferation and Activation

Hasan, Muhammad; Kallas, Esper G.; Thomas, Elaine K.; Looney, John; Campbell, M. H.; Evans, Thomas G.

doi:10.1089/107999000312513

Cited by 20 publications

(12 citation statements)

References 16 publications

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“…IL-15 induces lymphocyte proliferation and protects cells from apoptosis, thereby generating memory T cells (28) and anti-IL-15 can down-modulate lymphocyte proliferation (29). In our study, neutralization of IL-15 down-modulated SLA-induced IFN-γ secretion by PBMC from CL patients but had a weaker effect on PBMC from ML patients.…”

Section: Discussionmentioning

confidence: 99%

Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis

Carvalho

Passos

Bacellar

et al. 2007

Parasite Immunology

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Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN-gamma and TNF-alpha production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co-stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-gamma production in leishmania antigen-stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed antigen-specific IFN-gamma production, while in ML only anti-IL-2 suppressed IFN-gamma production. Finally, higher frequency of CD4+ T cells expressing CD28-, CD69+ and CD62L(low) were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.

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Section: Discussionmentioning

confidence: 99%

Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis

Carvalho

Passos

Bacellar

et al. 2007

Parasite Immunology

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“…In addition, in some studies, IL-15 (Immunex) and IL-12 (R&D Systems) were used at concentrations suggested in the literature. 24,25 For the studies, CD8 ϩ cells were either left unstimulated or stimulated with both anti-CD3 and anti-CD28 antibodies (R&D Systems). 23 The anti-CD3 antibodies (1 g/mL) were bound to 96-well round bottom plates for 2 hours at 37°C, washed twice with phosphate-buffered saline (PBS), and CD28 antibodies (1 g/mL) were then added.…”

Section: Subset Isolation and Cell Culturementioning

confidence: 99%

“…5 Culture supernatants were assayed for reverse-transcriptase (RT) activity on days 5 and 7. 24 The extent (percent) of CNAR was determined by comparing the average percentage of RT activity in supernatants from duplicate cocultures with the average RT activity in fluids from HIV-infected CD4 ϩ cells cultured alone. Bars indicate average suppression resulting from each treatment.…”

Section: Monocyte-derived Dendritic Cells Enhance Cnar In Hiv-infectementioning

confidence: 99%

Mature dendritic cells can enhance CD8+ cell noncytotoxic anti-HIV responses: the role of IL-15

Castelli

Thomas

Gilliet

et al. 2004

Blood

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The CD8 ؉ cell noncytotoxic anti-HIV response (CNAR) is associated with a longterm healthy clinical state in HIV-infected individuals. Over time CNAR is reduced concomitant with progression to disease. In studies to evaluate whether the interaction between CD8 ؉ cells and dendritic cells (DCs) could increase CNAR, CD8 ؉ cells from individuals who showed a decrease in this antiviral activity were cocultured with monocyte-derived dendritic cells matured with CD40 ligand. After coculture with these mature DCs, the CD8 ؉ cells showed an increase in CNAR greater than that observed with CD8 ؉ cells costimulated with CD3/CD28 antibodies. This antiviral response appeared to be mediated primarily by production of interleukin-15 (IL-15) by the mature DCs. Purified IL-15 also enhanced CNAR, whereas IL-12 showed no substantial effect. These studies provide another potential approach by which the immune system in HIV infection could be restored by cytokine therapy, particularly IL-15 administration. ( IntroductionCD8 ϩ cells from healthy HIV-infected individuals demonstrate a unique ability to suppress HIV replication without killing the infected cell. 1 The extent of this CD8 ϩ cell noncytotoxic antiviral response (CNAR) is reduced in infected individuals who progress to disease. [2][3][4][5] The cause for this loss in CNAR is not yet understood. One reason could be the decrease in a T helper 1 (TH-1) cell cytokine profile observed over time in HIV-infected individuals with a change toward the TH-2 type of immune response, that is, production of interleukin-4 (IL-4), IL-5, and IL-10. 6 TH-1 cell cytokines, particularly IL-2, help maintain CNAR; TH-2 cytokines inhibit its activity. 7,8 Since IL-2 production by lymphocytes results from their interaction with dendritic cells (DCs), 9 a compromise in DC function may be responsible for the loss of CNAR over time. In this regard, previous studies have shown that HIV-infected individuals exhibit a decrease in DC function and numbers circulating in the blood. 10,11 Another reason for reduced CD8 ϩ cell activity can be low CD4 ϩ cell counts, which also correlate with the loss of CNAR. 2,3,5 Therefore, CD40 ligand (CD40L), a surface protein expressed on CD4 ϩ cells following activation, may not be present at sufficient levels to mature DCs via CD40 to stimulate CD8 ϩ cell immune responses, specifically, CNAR. Upon activation by CD40L, dendritic cells mature and secrete IL-15 and IL-12. 12-16 IL-15 can regulate expansion and differentiation of CD8 ϩ cells, particularly the memory subsets of CD8 ϩ cells. 17-21 IL-12 induces the differentiation of T cells into TH-1 type cells that secrete large amounts of interferon-␥, which can also increase CD8 ϩ cell immune responses and CNAR. 7 Therefore, improving DC/T-cell interactions might restore or enhance CNAR in HIV-infected individuals. In evaluating this possibility, we studied whether dendritic cells, matured by CD40L, could enhance CNAR in CD8 ϩ cells from HIV-infected individuals. Patients, materials, and methods SubjectsHIV-infected s...

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“…This suggests that the observed deficiency in the measles-specific T-cell responses in infants is a more complex limitation of infant immune cells, likely to include other key cytokines. Like IL-12, IL-15 is an important cytokine made by activated antigen-presenting cells (APCs), which has both T-and B-cell stimulatory activity (30,43). Decreased IL-15, along with low IL-12 production, would decrease humoral immune responses as well as adaptive T-cell immunity, both of which are seen in infants immunized with measles vaccine.…”

Section: Introduction M Easles Remains a Substantial Cause Of Globalmentioning

confidence: 99%

Effects of Interleukin-12 and Interleukin-15 on Measles-Specific T-Cell Responses in Vaccinated Infants

et al. 2008

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Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-gamma release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-gamma release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L(+) T cells expressed IFN-gamma. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines.

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Effects of Interleukin-15 onIn VitroHuman T Cell Proliferation and Activation

Cited by 20 publications

References 16 publications

Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis

Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis

Mature dendritic cells can enhance CD8+ cell noncytotoxic anti-HIV responses: the role of IL-15

Effects of Interleukin-12 and Interleukin-15 on Measles-Specific T-Cell Responses in Vaccinated Infants

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