Maternal immunization with a soluble TCR-Ig chimeric protein: long term, V beta-8 family-specific suppression of T cells by maternally transferred antibodies.
Maternal transfer of TCR clonotypic Ab protected young NOD mice against the adoptive transfer of diabetes by the BDC 2.5 T cell clone. The effect of maternal anti-TCR Vbeta-8 Ab on T cell development and function has now been investigated. SJL/J mice, which lack TCR Vbeta-8, were immunized with soluble, chimeric D10 TCR-IgG1 containing Vbeta-8.2. The (SJL/J x AKR/J) F1 offspring of immunized female SJL/J mice were severely depleted of peripheral T cells bearing Vbeta-8 until 11 to 17 wk of age. The loss of Vbeta-8 expression did not appear to be due to modulation of cell surface TCR. Since the Vbeta-8+ T cell population was unperturbed in the (AKR/J x SJL/J) F1 offspring of D10 TCR-IgG1-immunized AKR/J mothers making D10 clonotypic Ab, the effect was immunologically specific. The deletion of Vbeta-8+ T cells had functional consequences. In the in vitro response to the superantigen, staphylococcal enterotoxin B, the usually observed participation of Vbeta-8.2+ T cells was largely suppressed, whereas the recruitment of Vbeta-3+ T cells remained unaltered. In control mice, T cell responses to the 134- to 146-residue peptide of conalbumin (pCA(134-146)) were biased toward use of Valpha-2/Vbeta-8.2 TCR. In D10 TCR-IgG1 maternally immunized (SJL x AKR/J) F1 mice, the T cell responses to pCA(134-146) were suppressed, and T cell lines derived from these in vitro were devoid of Vbeta-8.2 expression. With an increased understanding of TCR V gene usage in autoimmune diseases, similar strategies for the depletion of autoreactive T cells may become feasible in humans.
McKeever
U
U
Procept, Inc., Cambridge, MA 02139, USA.
Khandekar
S
S
Jesson
M
M
Newcomb
J
J
Gregory
P
P
Naylor
J
J
Haskins
K
K
Jones
B
B
D000818:Animals; D003207:Conalbumin / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000096:biosynthesis; D007108:Immune Tolerance / Q000235:genetics; D007112:Immunity, Maternally-Acquired / Q000235:genetics*; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D005810:Multigene Family / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D012995:Solubility; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D004768:Enterotoxins; D007106:Immune Sera; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D018089:Superantigens; D003207:Conalbumin; C031818:enterotoxin B, staphylococcal