Biomedical subjects

Jaime Imitola

Publications and source records attributed to Jaime Imitola.

21 records · Page 2Linked to original sources

PubMed2002

Interferon-beta treatment alters peripheral blood monocytes chemokine production in MS patients.

Chemokines direct the recruitment of leukocytes to inflammatory sites and may also participate in the regulation of cytokine production by naive T helper cells. Chemokine production by blood monocytes was investigated by intracytoplasmic staining in interferon-beta (IFN-beta)-treated multiple sclerosis (MS) patients, untreated MS patients, and healthy controls. Under unstimulated conditions, no differences in the production of interleukin-8 (IL-8), IFN-inducible protein 10 (IP-10), monokine induced by interferon-gamma (Mig), monocyte chemoattractant protein-1 (MCP-1), and monocyte chemoattractant protein-3 (MCP-3) were seen between untreated MS patients and controls. Chemokine production by monocytes following T cell activation was decreased in MS patients taking IFN-beta compared to controls and untreated MS patients. Unlike other chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha) production by monocytes was significantly decreased in untreated MS patients compared to controls, and IFN-beta treatment increased MIP-1alpha expression to the level seen in controls. In vitro addition of IFN-beta1b to peripheral blood mononuclear cells (PBMC) cultures tended to decrease the production of IL-8, IP-10, Mig, MCP-1, and MCP-3, but not of MIP-1alpha. These findings suggest that IFN-beta treatment may have a differential affect on chemokine production by monocytes. Longitudinal studies must be done to confirm these observations.

Adjuvants, Immunologic↗

PubMed2002

Th1 cytokines, programmed cell death, and alloreactive T cell clone size in transplant tolerance.

The Th1 cytokines IL-2 and IFN-gamma, which inhibit T cell proliferation and promote activation induced cell death, may be required to diminish alloreactive T cell numbers and to foster tolerance across full allogeneic barriers. However, we hypothesized that these cytokines might be dispensable when the alloreactive T cell clone size is relatively small, as is seen in recipients of minor-mismatched grafts. We show that alloreactive T cell clone size of C57BL/6 mice against multiple minor-mismatched 129X1/sv mice was approximately 4-9-fold smaller than that against MHC-mismatched BALB/c mice. In the MHC-mismatched combination, CD28-B7 blockade by CTLA4Ig induced long-term graft survival in wild-type recipients, but this treatment was ineffective in IFNgamma(-/-) or IL-2(-/-) recipients. In contrast, in the minor-mismatched combination, CTLA4Ig induced long-term allograft survival in wild-type, IFNgamma(-/-), and IL-2(-/-) recipients. Bcl-x(L) transgenic animals, which are defective in "passive" T cell death, are likewise sensitive to the effects of CTLA4Ig only in the setting of the minor-mismatch grafts. Therefore, the alloreactive T cell clone size is an important determinant affecting the need for Th1 cytokines and T cell death in tolerance induction. These data have implications for the design of tolerance strategies in transplant recipients with varying degrees of MHC mismatching.

Animals↗

PubMedDate not supplied

Neural stem cell biology may be well suited for improving brain tumor therapies.

Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel.

Brain Neoplasms↗