The DTH-initiating Thy-1+ cell is double-negative (CD4-, CD8-) and CD3-, and expresses IL-3 receptors, but no IL-2 receptors.
The elicitation of delayed-type hypersensitivity (DTH) requires an early-acting Thy-1+ cell that produces an Ag-specific, non-MHC-restricted factor that initiates DTH by sensitizing the local tissue for release of the vasoactive amine serotonin. We characterized the phenotype of this DTH-initiating cell by treating cells from sensitized mice with different antibodies and then either with rabbit C or anti-Ig panning or bead separation to deplete various subpopulations. We then transferred these cells i.v. into naive recipients that were challenged to elicit DTH. Our findings indicate that the early DTH-initiating cell is Thy-1+, Lyt-1+, CD4-, CD8- and CD3-, whereas the classical, late DTH effector T cell is Thy-1+, Lyt-1+, CD4+, CD8-, and CD3+. We hypothesize that DTH-initiating cells are primitive T cells with Ag receptors that can bind Ag without MHC-restriction. This hypothesis was supported by the finding that two different antibodies, that both bind T cell-derived Ag-binding molecules, eliminated the DTH-initiating, cell but did not affect the late component, MHC-restricted CD4+, CD3+ T cell. Additional experiments with antibodies against restricted determinants of the T-200 glycoprotein family (CD45R) showed that the early but not the late cell is positive for B220, which is usually present on B cells, and on some activated T cells. Also, the DTH-initiating cell is Il-2R-, but Il-3R+; whereas the late component DTH T cell is IL-2R+ and IL-3-. Our findings suggest that DTH-initiating cells may be Ag-specific lymphoid precursor cells that arise before final differentiation along the pathway leading to mature T or B cells. Our results indicate that antigen-specific Thy-1+, CD3-, CD4-, CD8- cells function in vivo to initiate DTH reactions.
Herzog
W R
WR
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Ferreri
N R
NR
Ptak
W
W
Askenase
P W
PW
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D000939:Epitopes / Q000032:analysis; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007377:Interleukin-3 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008808:Mice, Inbred CBA; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016185:Receptors, Interleukin-3; D013601:T-Lymphocytes / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D018800:Thy-1 Antigens