Nonencephalitogenic CD4-CD8- V alpha 2V beta 8.2+ anti-myelin basic protein rat T lymphocytes inhibit disease induction.
Recently there has been a number of reports suggesting that CD4-CD8- T cells participate in the processes of inflammatory reaction. In an attempt to delineate the distinctive functions of double negative (DN) T lymphocytes in an autoimmune-induced disease, we isolated and cloned such T cells, along with control CD4+ cells, from Lewis rats immunized with guinea-pig myelin basic protein in CFA. Both clones proliferated in response to the guinea-pig myelin basic protein and its synthetic encephalitogenic peptide, and expressed the same TCR V genes homologous to the mouse V alpha 2 and V beta 8.2 families that appear to be the defining entity of experimental autoimmune encephalomyeltis (EAE). Moreover, the TCR D and J region gene products of the DN cell were found to be similar to another encephalitogenic rat T cell clone. The two T clones did not differ markedly in their ability to produce TNF and IL-2 and to adhere to vascular wall-derived extracellular matrix- and laminin-coated plates. Surprising, therefore, was the finding that, although the CD4+ T lymphocytes were capable of inducing EAE, the DN cells did not elicit disease but rather inhibited subsequent EAE induction. Thus, TCR V alpha 2V beta 8.2 and its junctional region gene products are not the only prerequisite segment for a T cell to become encephalitogenic. We suggest that the important determinants of the T cell ability to induce disease are features of the T cell, other than or in addition to, the T cell receptor.
Lider
O
O
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Miller
A
A
Miron
S
S
Hershkoviz
R
R
Weiner
H L
HL
Zhang
X M
XM
Heber-Katz
E
E
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis* / Q000502:physiology; D016827:CD8 Antigens; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000517:prevention & control*; D005109:Extracellular Matrix / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell