Comparison of interferon-γ and interleukin-4 production by peripheral blood mononuclear cells and isolated T cells after activation with polyclonal t cell activators

1994 ◽  
Vol 8 (5) ◽  
pp. 277-283 ◽  
Author(s):  
Salvador Gonzalez ◽  
Lucinda Beck ◽  
Nevin Wilson ◽  
Hans L. Spiegelberg
Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1595-1603 ◽  
Author(s):  
K Welte ◽  
CA Keever ◽  
J Levick ◽  
MA Bonilla ◽  
VJ Merluzzi ◽  
...  

Abstract The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.


Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3696-3703 ◽  
Author(s):  
Carlo Chizzolini ◽  
Rachel Chicheportiche ◽  
Montserrat Alvarez ◽  
Casimir de Rham ◽  
Pascale Roux-Lombard ◽  
...  

Microenvironment molecular cues direct T helper (Th) cell differentiation; however, Th17 fate determination is still imprecisely understood in humans. To assess the role of prostaglandin E2 (PGE2) in Th expansion, we activated peripheral blood mononuclear cells by CD3 cross-linking. In the presence of exogenous PGE2, peripheral blood mononuclear cells produced higher interleukin-17 (IL-17), C-C chemokine ligand 20 (CCL20)/macrophage inflammatory protein 3α (MIP-3α), CXC chemokine ligand 8 (CXCL8)/IL-8, and lower interferon-γ and IL-22 levels than in control cultures. Exogenous PGE2 and IL-23 synergized in inducing IL-17, whereas indomethacin and IL-23 blockade drastically reduced IL-17 but not interferon-γ production. Furthermore, IL-1 but not tumor necrosis factor was absolutely required for IL-17 production. PGE2 doubled the frequency of CD4+ T cells producing IL-17 and within the CD4+ subset enhanced C-C chemokine receptor 6 (CCR6) and CCR4 while decreasing CXC chemokine receptor 3 (CXCR3) expression. Furthermore, in CD4+ T-cell lines, the production of IL-17 segregated with the CCR6+ subset. In the presence of CCR6+ compared with CXCR3+ Th cells, monocytes/macrophages produced much higher levels of matrix metalloproteinase-1, -3, and -9 but similar levels of CXCL10 and IL-1β. These results identify PGE2 and IL-23 as participating in the expansion of CD4+ T cells endowed with high IL-17 production capacity, which in turn favors monocyte production of mediators important for host defense and tissue destruction.


2006 ◽  
Vol 13 (5) ◽  
pp. 547-552 ◽  
Author(s):  
Rita Elizabeth Mascarenhas ◽  
Cláudia Brodskyn ◽  
Geisa Barbosa ◽  
Jorge Clarêncio ◽  
Antônio Souza Andrade-Filho ◽  
...  

ABSTRACT Evidence indicates that human T-cell lymphotropic virus type 1 (HTLV-1) infection leads to chronic immunosuppression and a greater susceptibility to infectious diseases. Spontaneous in vitro proliferation of peripheral blood mononuclear cells (PBMC) is an important immunological feature of HTLV-1-infected individuals. However, the association between spontaneous proliferation and immunosuppression is not clear. In this study, we evaluated the cellular immune responses of PBMC from 58 asymptomatic HTLV-1-infected individuals with PBMC showing or not showing spontaneous proliferation. Individuals with PBMC that spontaneously proliferated had increased proportions of CD4 T cells expressing CD45RO and dramatically reduced responses to recall antigens. In addition, frequencies of positive responses to recall antigens were also decreased in HTLV-infected individuals without spontaneous proliferation of PBMC. There was a polyclonal expansion of multiple T-cell receptor Vβ families of CD4+ T lymphocytes in patients with spontaneous proliferation. We observed that HTLV-1 induced an immunosuppression characterized by a decrease in the stimulation index to a recall antigen, even in individuals who did not present spontaneous proliferation. On the other hand, only patients with PBMC presenting spontaneous proliferation showed polyclonal activation and increased proportion of CD4 T cells expressing CD45RO.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1595-1603 ◽  
Author(s):  
K Welte ◽  
CA Keever ◽  
J Levick ◽  
MA Bonilla ◽  
VJ Merluzzi ◽  
...  

The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.


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