Recent studies have revealed that although the frog, Xenopus, expresses class II molecules throughout larval and adult life, tadpoles of this species do not express detectable class I antigens until they reach metamorphic climax. Hence, the larval frog provides a unique """"""""model of nature"""""""" (somewhat akin to humans with the """"""""bare lymphocyte"""""""" syndrome) with which to examine the biological roles of class I and class II antigens and class I- and class II-reactive T cells from an immunologic, ontogenetic, and phylogenetic perspective. The major goal of this proposal is to better understand the importance, in Xenopus, of class I antigen expression and anti-class I-reactive and class II-reactive T cells on: 1) lymphocyte-target cell interactions, 2) the establishment of self-tolerance and allotolerance, and 3) the ontogeny of the T cell repertoire. More specifically, I will use in vitro proliferative and cytotoxic assays, skin grafting between larvae and adults, embryonically created thymus/hematopoietic chimeras, and molecular biological techniques to address the following questions: 1. During adult life, do class I and class II gene products serve as target and restriction molecules of cytotoxic T cells? 2. In the absence of class I expression, do tadpoles have class I- restricted and anti-alloclass I-reactive cytotoxic T cells? 3. Do class II molecules serve as restriction elements for both helper and cytotoxic T cells of tadpoles? 4. Is there a relationship between the lack of class I expression and the ease with which tadpoles become tolerant of adult skin allografts (i.e., do class II disparities favor tolerance induction)? 5. If expression of class I molecules can be induced precociously in tadpoles, does this accelerate maturation of anti-class I- reactive T cells and facilitate development of autoimmunity? 6. Does the thymus play a critical role in the acquisition of the T cell repertoire, and when during ontogeny does it play this role? 7. What rearrangements of T cell receptor genes occur during ontogeny?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD007901-25
Application #
3484988
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-09-01
Project End
1993-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
25
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Kinney, Kevin S; Cohen, Nicholas (2009) Neural-immune system interactions in Xenopus. Front Biosci (Landmark Ed) 14:112-29
Robert, J; Sung, M; Cohen, N (2001) In vitro thymocyte differentiation in MHC class I-negative Xenopus larvae. Dev Comp Immunol 25:323-36
Robert, J; Menoret, A; Srivastava, P K et al. (2001) Immunological properties of heat shock proteins are phylogenetically conserved. Adv Exp Med Biol 484:237-49
Robert, J; Menoret, A; Basu, S et al. (2001) Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70. Eur J Immunol 31:186-95
Robert, J; Menoret, A; Cohen, N (1999) Cell surface expression of the endoplasmic reticular heat shock protein gp96 is phylogenetically conserved. J Immunol 163:4133-9
Carey, C; Cohen, N; Rollins-Smith, L (1999) Amphibian declines: an immunological perspective. Dev Comp Immunol 23:459-72
Robert, J; Cohen, N (1999) In vitro differentiation of a CD4/CD8 double-positive equivalent thymocyte subset in adult Xenopus. Int Immunol 11:499-508
Robert, J; Cohen, N (1998) Evolution of immune surveillance and tumor immunity: studies in Xenopus. Immunol Rev 166:231-43
Robert, J; Brown, D M; Pasquier, L D et al. (1997) Antibody cross-linking of the thymocyte-specific cell surface molecule CTX causes abnormal mitosis and multinucleation of tumor cells. Exp Cell Res 235:227-37