SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE : II. SYNERGY IN GRAFT-VERSUS-HOST REACTIONS PRODUCED BY BALB/C LYMPHOID CELLS OF DIFFERING ANATOMIC ORIGIN

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F1 hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F1 hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F1 recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types

SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE : III. EVIDENCE FOR INTERACTION BETWEEN TWO TYPES OF THYMUS-DERIVED CELLS

Two types of thymus-derived (T) lymphocytes have been shown to cooperate in the induction of graft-versus-host responses. One cell type is found in highest concentrations in the peripheral blood and lymph node, is extremely sensitive to anti-thymocyte serum (ATS) in vivo, and is probably part of the recirculating lymphoid cell pool (3). The second cell type, found in highest concentrations in the thymus and spleen, is relatively resistant to small doses of ATS in vivo. Both cell types are substantially depleted after neonatal thymectomy. Moreover, since synergism was also obtained using appropriate mixtures of cells from either parental strain in F1 hosts, it was possible to show that the nonrecirculating cells determined the specificity of the response and were probably the precursors of effector cells in this response. The recirculating T cell appeared to amplify this response. The implications of these data are discussed

SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE : V. DERIVATION BY MIGRATION IN LETHALLY IRRADIATED RECIPIENTS OF TWO INTERACTING SUBPOPULATIONS OF THYMUS-DERIVED CELLS FROM NORMAL SPLEEN

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F1 recipients, using the Simonsen spleen weight assay. Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-θ antibody and complement in vitro. These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived cells

SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE : IV. SYNERGY IN THE GVH REACTION QUANTITATED BY A MORTALITY ASSAY IN SUBLETHALLY IRRADIATED RECIPIENTS

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F1 recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells. Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy. The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells

THE EFFECTS OF HETEROLOGOUS ANTI-THYMOCYTE SERA IN MICE : III. HIGH SUSCEPTIBILITY OF GERMFREE MICE TO THE SUPPRESSIVE EFFECTS OF IGG FROM RABBIT ANTI-MOUSE THYMOCYTE SERUM

A quantitative graft-vs.-host (GVH) assay was used to compare the reactivity of spleen cells from germfree (GF) and conventionally reared (CV) mice against allogeneic tissue before and after treatment with rabbit anti-mouse thymocyte serum (ATS) and its IgG fraction (AT-IgG). AT-IgG produced a far greater and longer lasting suppression of this reactivity in GF than in CV mice. Moreover, CV mice recovered from suppression twice as rapidly as did GF mice. In both groups, the rate of recovery was exponential. These results suggest that recovery from the suppressive effects of ATS or AT-IgG was the result of generation of new cells. Transfer of mice born and initially reared in a conventional animal room to germfree isolators, with subsequent maintenance on the same diet that the germfree mice received, did not change the reactivity of their spleen cells in the assay used nor their susceptibility to AT-IgG. Removal of GF mice to a conventional animal room resulted in a prompt reduction in susceptibility to AT-IgG. The possibility that this might be related to the elaboration of a plasma factor affecting lymphocyte stability was discussed. Spleen cells taken from GF mice at various times after such "conventionalization" showed a transient but marked hyperreactivity to tissues of the allogeneic recipients. The amount of reduction in reactivity of spleen cells from such mice treated with AT-IgG was always proportional to the activity of spleen cells from comparable untreated mice. It was suggested that the increased reactions evoked should be ascribed to an adjuvant effect rather than to specific immunologic sensitization. Blood lymphocyte counts correlated very poorly with the state of suppression, confirming previous observations. It was also shown that while AT-IgG had little or no effect on blood granulocyte counts in both GF and CV mice, marked reductions in circulating granulocytes followed administration of AT-IgG during the period of increased granulocytopoiesis that resulted from conventionalization. This demonstrated that AT-IgG can produce functional impairment of target cells other than lymphocytes

SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE : I. SYNERGY IN GRAFT-VERSUS-HOST REACTIONS PRODUCED BY CELLS FROM NZB/BL MICE

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population

Predicting Obsessive-Compulsive Symptom Dimensions from Obsessive Beliefs and Anxiety Sensitivity

Cognitive models propose that obsessive-compulsive (OC) symptoms are maintained by maladaptive (obsessive) beliefs that give rise to anxiety and compulsive urges. Previous research, however, has found inconsistent relationships between obsessive beliefs and OC symptoms, and authors have called for further research to elucidate these associations. In addition, minimal research has examined the relationship between domains of anxiety sensitivity (AS) and OC symptoms. Accordingly, the present study examined the associations among OC symptom dimensions, obsessive beliefs, and AS domains using the most up-to-date measures of these constructs. The study included 699 undergraduate student volunteers who completed the Dimensional Obsessive-Compulsive Scale, Anxiety Sensitivity Index—3rd version, the Obsessive Beliefs Questionnaire, and the Depression Anxiety Stress Scale. Measures were aggregated from multiple web surveys. Regression analyses revealed that obsessive beliefs and anxiety sensitivity domains significantly predicted OC symptom dimensions above and beyond general distress, and that specific obsessive beliefs and anxiety sensitivity domains were uniquely associated with individual OC dimensions. The pattern of findings was generally consistent with what would be predicted from the cognitive model. Furthermore, the results provide preliminary evidence that such symptoms can be understood as unique dimensions of obsessions and compulsions with different cognitive and affective processes. Future studies should continue to examine these relationships in clinical OCD samples. The specific study findings as well as their implications for theory and for treatment programs, as tailored to address the heterogeneity of OCD, will be discussed.Bachelor of Art