RESUMO
High Mphi:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNgamma-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mphi expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mphi:T cell ratios found in many tumors.
Assuntos
Citocinas/biossíntese , Tolerância Imunológica/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Ativação Linfocitária/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Neoplasias/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Linfócitos T/efeitos dos fármacos , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígeno B7-1/genética , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Antígeno CTLA-4 , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/imunologia , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Citocinas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Interferon gama/biossíntese , Interferon gama/genética , Interferon gama/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Antígenos Secundários de Estimulação de Linfócitos/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Evasão TumoralRESUMO
Analysis of the immune system of spiny mice (Acomys cahirinus) has been limited. Originally grouped with Mus, Acomys has recently been placed closer to Meriones (gerbils). This study compared immunity in Acomys, Mus, and Meriones. Lymphocytes from all rodents examined proliferated in response to mitogen and superantigen stimulation. Only Mus T cells responded to anti-CD3 stimulation. Acomys, like Meriones, and Mus that express xid, did not respond to thymus-independent type 2 antigens. Flow cytometric analyses revealed that T cell-specific MAbs did not bind Acomys or Meriones lymphocytes. The B cell-specific anti-CD45R (B220) MAb detected all rodent B cells and revealed the absence of a CD45R(lo) subset in the peritoneal cavity of Acomys and Meriones. Bone marrow from Acomys and Meriones failed to reconstitute B cell function in SCID mice. Thus, in terms of immunity, Acomys appears to be more similar to Meriones than Mus.
Assuntos
Antígenos T-Independentes/imunologia , Murinae/imunologia , Linfócitos T/imunologia , Animais , Complexo CD3/imunologia , Citometria de Fluxo , Gerbillinae , Imunofenotipagem , Lipopolissacarídeos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos SCID , Mitógenos/imunologia , Mitógenos/farmacologia , Superantígenos/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Comparative analyses of the ability of lymphoid tissue to present the minor lymphocyte stimulatory (Mls) superantigen Mls-1a in vitro revealed that all tissues containing mature B cells, except peritoneal cavity (PerC) cells, induced Mls-1a-specific T cell activation. Irradiation and mitomycin C treatment, addition of IL-2 and IL-12, and neutralization of IL-10 and TGF-beta did not restore Mls-1a antigen presentation by PerC cells. Co-culture studies revealed that PerC cells actively suppress the T cell response to Mls-1a. PerC cells from severe-combined immune-defective (SCID) mice also suppressed this response indicating that nonlymphoid cells mediate this effect. These results suggest that in addition to antigen processing and presentation, resident peritoneal cavity cells may temper lymphocyte activation.
