Suppressor T cells induced by epidermally applied hapten are located in bone marrow.
Mice painted epidermally with trinitrochlorobenzene (TNCB) develop delayed type dermal hypersensitivity within five days, however, subsequent immunization with TNP-syngeneic antigens (TNP-H2k) does not generate CTLs to the same antigens. These studies were undertaken to determine what prevents development of the CTL. We report here, that a suppressor cell for CTL generation is found in the bone marrow (BM) of TNCB-painted mice. This suppressor cell is not present in spleens or lymph nodes, but is readily detected by adoptive transfer of BM cells. The cell responsible for suppression is an Lyt2+ (CD8+) T cell. Further studies with two monoclonal antibodies (one directed to a T cell suppressor factor [mAb 14-12], and the other directed to a suppressor T cell inducer factor [mAb 14-30]), demonstrated that the suppression could be reversed by either antibody when they were given prior to epidermal hapten painting. However, when each mAb was administered to recipients of BM cells from hapten painted donors, only mAb 14-12 reversed suppression of CTL generation. Examination of the number of resident BM cells revealed that TNCB-sensitized mice had 35% more cells than normal controls. When cultured in vitro with inactivated, syngeneic TNP-thymocytes, BM from normal mice readily developed TNP-self specific CTL, whereas whole BM from hapten-painted mice did not. The inability to generate CTLs was found to be attributable to suppressor cells, since BM cells from hapten-painted mice prevented CTL development by splenic T cells in culture. BM cells from normal mice did not suppress CTL generation. Suppression in vitro was not overcome by the presence of exogenous IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Kuo
T S
TS
Section of Immunology, Cleveland Clinic Foundation, Ohio 44195.
Matriano
J
J
Ferguson
T A
TA
Battisto
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells; D016827:CD8 Antigens; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010853:Picryl Chloride / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D010853:Picryl Chloride