Helen C. O'Neill

A subset of T cell receptors associated with L3T4 molecules mediates C6VL leukemia cell binding of its cognate retrovirus

We show here that the interaction of a radiation leukemia virus-induced thymoma, C6VL, with its cognate retroviruses occurs in the vicinity of the T cell receptor (TCR). While an anti-clonotypic antibody completely inhibits this interaction, antibodies specific for another T cell receptor complex determinant, L3T4, only partially inhibit the cell-retrovirus interaction. Several antibodies to more abundant cell-surface determinants (T200, Ly15, H-2Db) do not inhibit this interaction. Under capping conditions, either of the antibodies to L3T4 or TCR epitopes modulate virus binding receptors from the surface of C6VL/1 cells. L3T4 and the TCR do not comodulate significantly on the surface of C6VL/1 cells. These experimental findings implicate the existence of rare TCR-L3T4 complexes on C6VL/1 cells, and the involvement of these complexes in the binding of C6VL/1 to its cognate retrovirus. In addition, the clonotypic anti-TCR antibody inhibits C6VL/1 cell proliferation at concentrations that block its binding to its produced retroviruses.

A Role for Early Cytotoxic T Cells in Resistance to Ectromelia Virus Infection in Mice

Ectromelia virus-specific cytotoxic T (Tc) cell precursors were present in the draining popliteal lymph node of all strains of mice tested at 2 to 3 days after footpad inoculation of a high dose (10(5) p.f.u.) of the virulent Moscow strain of ectromelia virus. To detect this response it was necessary to culture lymph node cells from infected mice in the presence of T cell growth factors and to use the more sensitive neutral red assay for measuring cytotoxicity. Cells with lytic activity were virus-specific, major histocompatibility complex-restricted TC cells. C57BL/6J resistant mice, which express a single dominant gene conferring innate resistance had virus-specific TC cell precursors 1 to 2 days sooner than did susceptible BALB/b mice. This TC cell-mediated immune response early after infection could account for the barrier to virus dissemination known to operate 1 to 2 days after infection to slow virus passage into the lymphoreticular system.

Isolation of a thymus-homing Lyt-2−, L3T4− T-cell line from mouse spleen

We have selectively isolated and transformed a population of T-cell-receptor+, Lyt-2-, L3T4- cytotoxic T cells from mouse spleen following stimulation in vivo with a radiation leukemia virus-induced thymoma, C6VL/1. The two sublines analyzed here were found to induce tumors with primarily thymic involvement and one of these has been shown to have specific homing capacity for the thymus. Properties displayed by this cell line are evidence that T cells do exist in peripheral lymphoid tissue which can traffic back to the thymus and that Lyt-2-, L3T4- immature T cells can enter peripheral lymphoid organs.

Resistance to ectromelia virus infection in mice. Analysis of H-2-linked gene effects.

SummaryThe mechanism for resistance to ectromelia infection has been investigated in B6 and B10 congenic strains of mice which carry different alleles at theH-2 major histocompatibility locus. Greater susceptibility in some B10 congenic strains of mice has been associated with higher viral titres in the draining popliteal and inguinal lymph nodes as well as spleen at 3 days post infection. T cells which develop cytotoxic function following in vitro culture in the presence of T cell growth factors have also been detected in the popliteal lymph nodes of B6/B10 congenic strains of mice as early as 3 days post infection. Greater cytotoxicity has been detected in cultures of cells from resistant B6/B10 mice than from the susceptible B10 congenic strain B10.G, or other semi-resistant B10 congenic strains which differ at theH-2 locus. The early activation of T cells appears to be underH-2 gene control and activated T cells may play an “early” role in controlling viral replication within the lymphoid system.

Effects of anti-class I antibodies on proliferation of murine T lymphocytes

Antibodies specific for the murine Class I H-2K/D molecules have been analyzed for their effect on the proliferation of murine T cells. Several antibodies specific for both private and public determinants have been found to inhibit lectin-mediated T-cell proliferation. These same antibodies do not noticeably effect growth factor-dependent proliferation of activated T cells and have been found to stimulate rather than inhibit alloantigen-induced proliferation of T cells. Taken together these results suggest that Class I molecules may have some functional role in the early events of T-cell stimulation/proliferation, although the mechanisms for antibody effect may be different for T cells stimulated in different ways.

Natural Anti-Self Reactivity Which Maps to MHC Class I Genes

Responder spleen cells of [B10.A(5R) x B10.A(2R)]F1 hybrid mice cultured in vitro with irradiated parental spleen cells, generate a cytotoxic T cell response which maps to the H-2Dd and H-2(K-I)b genes of the B10.A(5R) parent. Specific reactivity of (5R x 2R) cells to B10.A(5R) parental (P) stimulators and not to F1 hybrid or B10.A(2R) stimulators was also demonstrated as an F1 anti-P proliferative response. Generation of a (5R x 2R) anti-5R response has also been noted during 2 degrees in vitro anti-viral cytotoxic responses where (5R x 2R) cells from either ectromelia or Sendai virus primed mice have been stimulated in vitro with infected 5R cells, but not when stimulated with infected 2R or (5R x 2R) cells. The generation of these responses is dependent on the use of parental stimulators for F1 hybrid cells during in vitro culture. All data is consistent with the hypothesis that (5R x 2R) F1 cells are not tolerant of 5R cells, and of the 4-fold higher level of Class I H-2Kb/Dd antigens which they express.