Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

Prud’homme, Gérald J.; Colle, Eleanor; Fuks, Abraham; Guttmann, Ronald D.

doi:10.2337/diab.36.2.237

Cited by 9 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, it is possible that such expression, although lasting for at least 24 h in this study, may represent a transient event, a fact supported by the findings of Scheymius et al on rat keratinocytes [24]. Indeed, the role of Class II MHC molecules in the pathogenesis of Type 1 diabetes has been emphasized by several investigators [25,26]. In the latter report, Prud'homme et al were able to inhibit islet cell antigen recognition by T-cells in the BB rat by a monoclonal antibody directed against the Class II D region of the rat MHC (analogous to human DR).…”

Section: Discussionsupporting

confidence: 63%

Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line in vitro following exposure to gamma interferon

et al. 1988

View full text Add to dashboard Cite

A study of Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line (RINm5F) was performed using monoclonal antibodies and immunoperoxidase techniques. RINm5F cells were incubated with different concentrations of gamma interferon. RINm5F cells exhibit low levels of Class I molecules and are normally devoid of Class II gene products. Upon exposure to gamma interferon, RINm5F cells showed a dramatic increase in Class I expression. This expression was homogenous and could be detected on all cells after 18 h of incubation with as little as 1 unit/ml of interferon. In contrast, de novo Class II expression was not homogeneous and required 36 h of incubation with 10 units/ml of interferon. The number of RINm5F cells expressing Class II antigens was dose- and time-dependent. Interferon treatment did not affect the morphology of RINm5F cells as determined by ultrastructural analysis. Withdrawal of interferon from the culture medium for as long as 78 h diminished but did not abolish the expression of Class I and Class II molecules already induced. The ability of interferon to enhance expression of Class I gene products and induce de novo expression of Class II molecules on B-cell-derived RINm5F cells supports the hypothesis that aberrant expression of major histocompatibility complex gene products on pancreatic B cells may be an important factor in triggering the immune response in Type 1 (insulin dependent) diabetes mellitus.

show abstract

Section: Discussionsupporting

confidence: 63%

Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line in vitro following exposure to gamma interferon

et al. 1988

View full text Add to dashboard Cite

show abstract

“…MHC genes encoding class I and II antigens have been successfully studied employing this method [17,18], however, no attempts have been reported earlier on the use of this method for studying cell mediated B cell autoreactivity in vitro. RIN cells have been used as antigen source and target cells in a series of studies designed to studyT lymphocyte mediated autoreactivity [12][13][14][19][20][21][22] and concern about the influence of the foreign MHC haplotype of the RIN cells has been raised [13,14]. This report describes the first experiments designed to overcome this problem by creating RIN cells syngeneic for a single MHC gene.…”

Section: Discussionmentioning

confidence: 99%

Transfected rat islet tumour cells express mouse major histocompatibility complex class I antigens functionally

Serup¹,

Schøller

1989

Diabetologia

View full text Add to dashboard Cite

Summary.Rat insulinoma cells clone 5AH-B, were transfected by electroporation with the gene encoding the mouse major histocompatibility complex class l antigen H-2K b, whereupon stable transfectants were selected and analysed. Data from flow cytometric analyses using three different H-2K h specific monoclonal antibodies and functional assays using H-2K b specific alloimmune cytotoxic Tcells revealed that the encoded H-2 antigen was expressed in a functional manner. Similar experiments employing the monoclonal antibody OX-18, which recognizes rat major histocompatibility class I molecules, and xenoimmune cytotoxic T cells specific for the endogenously expressed RT1 g antigen showed that functional expression of the RTI g antigen was maintained. However, a down-regulation of the expression was observed in H-2K h positive transfectants, whereas normal expression was retained in K b negative transfectants. The function of the native promoters of both the endogenous and the transfected class I genes was found to be preserved in the transfectants as assessed by the response to stimulation with interferon-'t. The present study was unable to confirm the reports of RIN specific lysis by T cells from multiple low dose streptozotocin diabetic mice. Even in the presence of the syngeneic restriction element no lysis was observed. We conclude, that rat insulinoma cells clone 5AH-B, are able to integrate a foreign class I antigen gene and express the encoded product functionally. The data also suggest the possibility of creating major histocompatibility antigen positive rat insulinoma cells which are RT1 g negative. Such transfectants will be of great potential value for the dissection of cell mediated B cell destructive pro- An X-ray induced rat insulinoma [1] has given rise to a series of cell lines [2-4] very widely used for experimental diabetes research. Nevertheless, for some immunological studies these cell lines often pose a serious problem. They all share the rare rat major histocompatibility complex (MHC) haplotype RTI g of the New England Deaconess Hospital (NEDH) rat which harboured the original tumour and, as such, they constitute either an allogeneic or xenogeneic cell line when used in studies of cell mediated B cell destruction. This severely limits their use. Consequently it would be a great advantage if it was possible to change them into "syngeneic" cells of a desired MHC haplotype. In the present study we therefore introduce an efficient method for transfection of the rat insulinoma cell line RIN 5AH-B-t2 (RIN). Using this method we were able to study whether RIN cells could express an introduced H-2 class I antigen in a functional manner, and how expression possibly affects the recognition of RIN cells by lymphocytes isolated from multiple low dose streptozotocin diabetic mice. Materials and methods Animals16-week old C3H and C57B1/'6 mice were purchased from the Charles River Breeding Laboratories, (Sulzfeld, FRG) and were allowed to acclimatize for at least a week before use in experimental work. NEDH ra...

show abstract

“…This lack of pure antigen has severely hampered the demonstration and isolation of P-cell-specific T cells. However, cell-mediated cytotoxicity against pancreatic P cells (5,6,7, 9, lo), and the isolation of putative P cell-specific T cells ( 12,14) and T-cell hybridomas ( I 3,14) have been reported. In the present study we have attempted to raise P-cell-specific T cells in a xenogeneic system.…”

mentioning

confidence: 99%

Mouse cytolytic T cells reactive with rat islet tumour RIN 5AH‐B cells

Schøller¹,

Rubin²

1990

APMIS

View full text Add to dashboard Cite

Insulin dependent (type 1) diabetes mellitus is considered to be an autoimmune disease characterized by a specific destruction of the insulin‐producing pancreatic β cells. We have explored the possibilities of raising T cells specific for putative pancreatic β‐cell autoantigens using a xenogeneic system. Mouse T cells were induced against the rat insulinoma cells RIN 5AH‐B (RIN) and tested for their specific reactivity. No MHC class II‐restricted β‐cell‐specific helper T‐cell reactivity could be detected within the bulk cultures as measured by proliferation, but a remarkably high cytotoxicity against the RIN cells was observed. The target antigen on the cell surface recognized by the generated cytotoxic T cells was shown to be the rat class I major histocompatibility antigen RT18, and not a β‐cell or tumour cell‐specific antigen associated with RIN cell MHC molecules. Our results demonstrate that it is feasible to evoke a xenogeneic T‐cell response against the RIN cells. However, the mouse T cells recognize a dominant epitope present on the expressed rat class I major histocompatibility antigen RT1A8 and not a β‐cell‐specific antigen. Hence, we conclude that it appears most unlikely that β‐cell‐specific T cells can be raised in the xenogeneic system.

show abstract

Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

Cited by 9 publications

References 7 publications

Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line in vitro following exposure to gamma interferon

Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line in vitro following exposure to gamma interferon

Transfected rat islet tumour cells express mouse major histocompatibility complex class I antigens functionally

Mouse cytolytic T cells reactive with rat islet tumour RIN 5AH‐B cells

Contact Info

Product

Resources

About