Complete Freund's Adjuvant

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J Immunol. 1993 Mar 1;150(5):2072-80. Links

Complete Freund's Adjuvant aka CFA ... induced T cells ... apparently prevent the development and adoptive transfer of diabetes in non-obese diabetic mice.

Qin HY, Sadelain MW, Hitchon C, Lauzon J, Singh B.

Department of Immunology, University of Alberta, Edmonton, Canada.

T1 or Insulin-dependent diabetes mellitus is a condition of above average blood glucose concentration (AABGC) that is usually characterized by down-regulation of the quantity and/or mass of insulin-producing beta-cells in the islet of Langerhans of the pancreas.

The condition in non-obese diabetic (NOD) mice can be prevented by a single injection of CFA.

This study explores the cellular basis and the time course of the reduction in AABGC.

Since CFA contains a mycobacterial cell wall that has adjuvant property, the role of mycobacteria in young NOD mice was investigated.

Mice injected with Mycobacterium tuberculosis or Mycobacterium bovis (BCG vaccine) at 4 wk of age were also found to be prevented from developing AABGC.

It was found that prevention of AABGC is only achieved by administration of CFA between 4 and 10 wk of age.

Draining lymph node cells or spleen cells from CFA-treated NOD mice transfer the prevention of AABGC. Adoptive transfer of spleen cells from CFA-treated mice with spleen cells from acutely diabetic mice delayed the induction of any AABGC condition into irradiated recipient mice. CFA-treated old NOD mice were also resistant to passive transfer of any AABGC condition by spleen cells from acutely diabetic mice.

Depletion of the Thy 1.2+ cells or CD4(+)-bearing T cells abrogated the prevention of developing AABGC. However, diabetes can be induced in the 'treated' mice by cyclophosphamide treatment.

It was also found that thymocytes from NOD mice responded only weakly to mitogen Con A. CFA treatment, however, restored the ability of these cells to respond to Con A. Finally, the results apparently suggest that T cells induced after CFA treatment of NOD mice prevent both the induction & effector phases of the AABGC condition.

http://www.ncbi.nlm.nih.gov/pubmed/8436836

UNdrugTREATED rare but well defined ...HOW ?

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What is CFA ? ? ?

'Complete Freund's Adjuvant' is an antigen solution emulsified in mineral oil, used as an immunopotentiator (booster of the immune system).

Forms

The so-called complete form (CFA) is composed of inactivated and dried mycobacteria, usually Mycobacterium tuberculosis (the pathogenic agent of tuberculosis).

The so-called incomplete form (IFA) is the same adjuvant, but without the mycobacterial components.

Eponym

It is named after Jules T. Freund (1890-1960), Hungarian-born American immunologist.

Regulation

Freund's adjuvant is effective in stimulating cell-mediated immunity and may lead to the potentiation of the production of certain immunoglobulins, but this effect depends on the animal model used. Its use in humans is forbidden, due to its toxicity. Even for animal research there are currently guidelines associated with its use, due to its painful reaction and potential for tissue damage. Injections of CFA should be subcutaneous or intraperitoneal, because intradermal injections may cause skin ulceration and necrosis; intramuscular injections may lead to temporary or permanent muscle lesion, and intravenous injections may produce pulmonary lipid embolism.

Effects

When administered to mice, in some laboratory experiments Freund's complete adjuvant was said to have prevented juvenile-onset diabetes^[1][2] and combined with prepared spleen cells was said to have reversed it.^[3] In 2006 these claims were challenged by the findings of several other researchers.^[4] Although newspapers have described the 2006 findings as confirming the earlier experiments,^[5] in substantial ways they conflict with them. A report from NIH was released on November 23, 2006 in Science confirming the participation of spleen cells in reversing end-stage diabetes.^[6][7]

It has also been investigated in an animal model of Parkinson's disease.^[8]

Mechanism

The adjuvant is known to stimulate production of tumor necrosis factor, which is thought to kill the T-cells responsible for the autoimmune destruction of the pancreatic Beta cells. Still in question is whether the regrowth of functional insulin-producing cells occurs due to differentiation and proliferation of existing pancreatic stem cells, or whether the injected spleen cells re-differentiate to an insulin producing form. Denise Faustman, whose work has been central to developing the protocol, has suggested that both mechanisms may play a role. However, in experiments to verify and examine her work, Suri reported that DNA-based evidence yielded no sign of spleen cell derivatives in pancreatic islet Beta cells analyzed after treatments.^[9]

External links

• Recommendations for Use and Alternatives to Freund's Complete Adjuvant. University of Iowa

References

1. ^ Sadelain, M.W., et al. (1991), "Prevention of type I diabetes in NOD mice by adjuvant immunotherapy", Diabetes 39(5): 583-589, <http://diabetes.diabetesjournals.org/cgi/content/abstract/39/5/583>
2. ^ Qin, H.Y., et al. (1993), "Complete Freund’s adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice", J. Immunol. 150: 2072–2080, <http://www.jimmunol.org/cgi/content/abstract/150/5/2072>
3. ^ Kodama, S., et al. (2003), "Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice", 'Science' 302: 1223-1227, <http://www.sciencemag.org/cgi/content/abstract/302/5648/1223>
4. ^ Couzin, J. (2006), "Diabetes Studies Conflict on Power of Spleen Cells", Science 311: 1694, <http://www.sciencemag.org/cgi/content/full/311/5768/1694>
5. ^ Kolata, G. (2006 March 25), "A Controversial Therapy for Diabetes Is Verified", New York Times, <http://www.nytimes.com/2006/03/24/health/24diabetes.html>
6. ^ New data from NIH lab confirms protocol to reverse type 1 diabetes in mice, BiologyNewsNet, November 2006
7. ^ Philip E. Ross, Putting Up with Self, Scientific American, November 12, 2006
8. ^ Armentero MT, Levandis G, Nappi G, Bazzini E, Blandini F (2006). "Peripheral inflammation and neuroprotection: systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease". Neurobiol. Dis. 24 (3): 492–505. doi:10.1016/j.nbd.2006.08.016. PMID 17023164.
9. ^ Suri, A., et al. (2006), "Immunological Reversal of Autoimmune Diabetes Without Hematopoietic Replacement of β Cells", Science 311: 1778-1780