Structural correlates of idiotopes.
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Biomedical subjects
Publications and source records attributed to C T Lutz.
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The number of alloreactive helper T lymphocytes (HTL) which cooperate with cytolytic T lymphocytes have been quantified in a sensitive limit dilution system. Approximately 1 in 330 splenic T lymphocytes developed helper activity in response to alloantigen of a single haplotype. Most HTL appeared to cooperate nonspecifically with the cytolytic cells. A significant number of alloreactive HTL precursors recognized H-2 K or D alloantigen, but roughly 6-fold more HTL precursors responded to H-2 I, and roughly 20-fold more responded to non-H-2, presumably Mls, alloantigen. These results support the hypothesis that alloantigen encoded by the H-2 I and non-H-2 Mls regions preferentially stimulate helper T lymphocytes, while alloantigens encoded by the H-2 K and D regions preferentially stimulate cytolytic T lymphocytes.
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Cortisone-resistant (CR) thymocytes did not generate cytolytic activity toward H-2 K or D alloantigen unless they were also stimulated by H-2 I or non-H-2 alloantigens, even though spleen cells generated brisk cytolytic activity toward H-2 K or D alone. Backstimulation by stimulating strain T lymphocytes accounted for neither the response of spleen cells toward H-2 K or D alloantigen nor the response of CR thymocytes to a full set of alloantigens. In addition, lack of non-T accessory cells did not account for the CR thymocyte pattern of reactivity. Rather, CR thymocytes appeared to be relatively deficient in helper T lymphocytes (HTL). CR thymocytes generated specific cytolytic activity toward H-2 D alloantigen when T cell growth factors (TCGF) or cloned alloreactive helper T lymphocytes were added to culture. CR thymocytes contained fewer HTL precursors detected at limit dilution than spleen cells did. Thus spleen cells generated cytolytic activity toward class I alloantigens alone, but under the same culture conditions CR thymocytes had to be stimulated by both class I and class II alloantigens. Class II alloantigens may be required to stimulate cytolytic activity only under culture conditions in which class I-reactive HTL are not sufficient to provide a minimal threshold of help.
We examined the role of accessory cells that cooperated with the cloned cytolytic T cell line, L3. Accessory cells and T cell growth factors (TCGF) acted synergistically to stimulate cloned L3 CTL to grow and produce cytolytic activity. Accessory cells were non-T, radioresistant, plastic adherent M phi-like cells that interacted with cloned L3 CTL via soluble factors. Peritoneal M phi, at low density, also cooperated with L3 cells but at high density, inhibited L3 cells. Both accessory and inhibitory M phi acted upon L3 CTL without the intervention of other T lymphocytes or nonadherent cells. Other published reports indicate that M phi may promote cytolytic activity indirectly, amplifying TCGF production by helper T lymphocytes. This report indicates that M phi may also promote cytolytic activity directly, amplifying the response of CTL to TCGF.
A system is presented that may simplify the study of accessory cell requirements for CTL generation. Cortisone resistant (CR) thymocytes containing alloreactive CTL precursors do not respond to allogeneic tumor cells unless non-T accessory cells are added to culture. In addition, splenic T cells do not respond to allogeneic tumor cells in the absence of non-T accessory cells. These accessory cells share several properties of macrophages.