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C C McCombs

Publications and source records attributed to C C McCombs.

32 records · Page 2Linked to original sources
PubMed1983

Effect of androgen therapy on survival and suppressor cell activity in aged NZB/NZW F1 hybrid mice.

Male NZB/NZW F1 hybrid (B/W) mice survive their first year of life and die of lupus nephritis or lymphoid malignancy during the second year. Androgen therapy, even if delayed until 9 months of age, improves survival considerably. We report here that androgen therapy in aged B/W mice is associated with improved cell-mediated immune function as well as increased survival. Androgen treated mice have significantly augmented spleen cell responses to phytohaemagglutinin (PHA) and a decreased incidence of abnormal splenic suppressor activity. These results suggest that androgen may prolong survival in B/W mice in part through an effect on abnormally suppressive regulatory cells that impair T lymphocyte function.

Aging↗
PubMed1982

Lymphocyte abnormality associated with HLA-B8 in healthy young adults.

We have reported that abnormal lymphocyte function in Sjogren's syndrome occurs almost exclusively in patients with HLA-B8. We now report that most clinically normal individuals with this antigen have a similar impairment of cellular immunity. This finding suggests that the lymphocyte abnormality in Sjogren's syndrome is not secondary to the disease process or medication and might have primary etiological significance. The lymphocyte abnormality is expressed as a decreased proliferative response to suboptimally stimulating concentrations of phytohemagglutinin (PHA) and concanavalin A (Con A). In contrast, the response to optimally stimulating concentrations of PHA and Con A is unaffected. The imparied mitogen responsiveness appears to be intrinsic to the T lymphocytes, as it can be demonstrated in purified T cell preparations.

Adult↗
PubMed1982

Human alveolar macrophages suppress the proliferative response of peripheral blood lymphocytes.

Human alveolar cells were isolated from bronchopulmonary lavage fluids obtained from patients undergoing clinically indicated bronchoscopy. Alveolar cells strongly suppressed the proliferation of peripheral blood lymphocytes in response to mitogens and antigens. Separation of the alveolar cells into adherent and nonadherent fractions indicated that the suppression was mediated by the adherent cells, or alveolar macrophages. Indomethacin at least partially relieved suppression, suggesting the involvement of prostaglandin synthesis. The suppression could be duplicated by supernatants obtained from unstimulated cultures of alveolar cells. Some specificity of suppression was apparent, in that not all proliferating cells were suppressed. T lymphocytes may be more readily suppressed than B lymphocytes, and the most susceptible cells may be a subpopulation of T lymphocytes.

Cell Adhesion↗
PubMed1982

Accelerated mixed lymphocyte culture test potentially useful for cadaver organ transplantation.

The mixed lymphocyte culture (MLC) test accurately predicts the strength of rejection of transplanted organs. Ironically, the MLC test can seldom be used in cadaver organ transplantation, where it would be most useful, because the test takes 4 to 6 days to get results. We have developed an accelerated MLC test using precultured cells, which gives interpretable results in 24-48 hr. Precultured cells become responsive to T cell growth factor, reflecting the generation of lymphoblasts during preculture. When 7 consecutive pairs of subjects were compared in the fast and conventional MLC tests, the response at 48 hr in the fast MLC was significantly correlated with the response in the conventional MLC test on days 5 and 6 (P less than 0.01). Precultured cells can be frozen in liquid nitrogen without loss of accelerated responsiveness and significant proliferation is also observed within 24 to 48 hr using frozen cultured cells. Thus, preliminary culture followed by cryopreservation provides the basis for a clinically useful fast MLC test for cadaver organ transplantation.

Animals↗
PubMed1981

Increased prevalence of HLA-B27 in patients with ectopic ossification following traumatic spinal cord injury.

The histocompatibility antigen HLA-B27 was determined in 43 patients with post-traumatic spinal cord injury (SCI). The prevalence of B27 was significantly increased in the SCI patients with ectopic ossification. Five of 21 patients with ectopic bone had B27 compared to none of the 22 patients without ossification (P = 0.021). This finding indicates that HLA-B27 is a genetically determined risk factor for the development of heterotopic ossification following injury to the central nervous system. Future studies may determine that HLA-typing can identify a group of patients at a high risk of a disabling complication of SCI who should be treated prophylactically to prevent ectopic bone.

Adult↗
PubMed1979

Suppressor cells and immunodeficiency in (NZB x NZW)F1 hybrid mice.

Old (15-20 month) male (NZB x NZW)F1 (B/W) mice have severely impaired spleen cell reactivity to phytohemagglutinin (PHA), a mitogen which stimulates mainly T lymphocytes. Spleen cells from old mice markedly suppressed the PHA response of splenocytes from young (3-4 month) B/W males. Similar suppressor activity was not present in the spleens of old mice of four nonautoimmune strains. The suppressor activity of old B/W spleen cells was mediated by a nonphagocytic, radioresistant, mononuclear leukocyte. Although this cell was eluted in the "T lymphocyte" fraction of nylon wool colums, it was not sensitive to treatment with anti-Thy-1 antiserum and complement. Suppressor activity was lost after 18 h incubation at 37 degrees C in tissue culture medium. Supernatants of these overnight cultures had no suppressive effect on fresh young B/W spleen cells. Old B/W spleen cells suppressed PHA reactivity more than concanavalin A or lipopolysaccharide reactivity. Kinetic studies demonstrated an increasing suppression with time over 72 h of culture. This study demonstrate that the severely impaired PHA reactivity of old B/W mice is mediated, at least in part, by active suppression.

Aging↗
PubMed1979

Subfractionation of human peripheral blood lymphocytes on the basis of their surface properties by partitioning in two-polymer aqueous phase systems.

Partitioning of cells in dextran-poly(ethylene glycol) aqueous-aqueous two-phase systems is a sensitive method for separating cells and for obtaining information on their surface properties. Highly purified lymphocytes were obtained by velocity sedimentation of human peripheral blood mononuclear cells and fractionated by countercurrent distribution (CCD, a multiple-step extraction procedure) in a charged two-polymer aqueous phase system. The lymphocytes remained viable after separation (order of 90%) and the E-rosetting cells responded (after adding back monocytes) to mitogens (PHA, Con A, PWM). Not only was the total lymphocyte population found to be highly heterogeneous (as evidenced by a broad and skewed distribution curve), but we were able to show that cells that rosetted with E, or had complement or Fc receptors were composed of additional subpopulations as well. The bulk of complement-receptor-bearing cells had the lowest partition coefficient (K), E-rosetting cells an intermediate K, and Fc-receptor-containing cells the highest K. The largest lymphocytes were among the subpopulation having the highest K and neither responded to T cell mitogens nor rosetted with E. Our results thus demonstrate that human peripheral blood lymphocytes can be subfractionated by CCD. The fractions are differentially enriched with lymphocyte subpopulations having characteristic surface markers and functional abilities.

Animals↗
PubMed1978

Acceleration of human lymphocyte activation after preliminary culture.

Human peripheral blood mononuclear cells which are precultured in tissue culture medium containing 5% fetal calf serum (FCS) have markedly augmented reactivity to a suboptimal concentration of phytohemagglutinin (PHA). The augmentation of response is due in part to an acceleration of lymphocyte activation. Precultured cells also respond in an accelerated manner to allogeneic cells. The augmentation is apparent after 24 hr of preliminary culture, and reaches a maximum at 4 to 7 days. Kinetic studies of the culturally augmented PHA response indicate that an increased number of reactive lymphocytes rather than an increased rate of proliferation accounts for the effect. Adding fresh cells to the precultured cells does not suppress their augmented response. When human serum is substituted for FCS in the preliminary culture, the augmentation of response does not occur. Serum-mixing experiments indicate a suppressive effect of human serum. These studies may be relevant for understanding immunologic mechanisms related to transplantation and autoimmunity.

Animals↗
PubMedDate not supplied

Inhibition of polyamine synthesis suppresses human lymphocyte proliferation without decreasing cytokine production or interleukin 2 receptor expression.

Difluoromethylornithine (DFMO) irreversibly inhibits ornithine decarboxylase (ODC), a crucial enzyme in polyamine synthesis, and impairs mitogen-induced lymphocyte proliferation. To examine the mechanism of action of DFMO, we studied the effect of this ODC inhibitor on lymphokine production and interleukin 2 (IL 2) receptor expression. DFMO decreased thymidine uptake of peripheral blood mononuclear cells stimulated by the mitogens phytohemagglutinin, concanavalin A, phorbol myristate acetate and ionomycin 60-70% compared with untreated cells, and the inhibition could be completely reversed by 10 mM spermidine. DFMO had no effect on IL 1 production by monocytes exposed to silica particles. Concentrations of IL 2 increased 7-fold in DFMO-treated, PHA-stimulated PBMC cultures, compared with untreated cells; whereas IL 2 receptor expression as measured by the anti-Tac monoclonal antibody was not affected by the inhibition of ODC. Mixing experiments using cells cultured with or without DFMO indicated that the inhibition by DFMO was not mediated by suppressor cells. Our results strongly support the concept that polyamines are required for a relatively late event in lymphocyte activation occurring after the interaction of IL 2 and its receptor.

Biogenic Polyamines↗
PubMedDate not supplied

HLA haplotypes in a family with multiple cases of rheumatoid arthritis.

Population studies have identified the histocompatibility antigen HLA-DR4 to be a genetic marker of significantly increased risk for the development of rheumatoid arthritis (RA). Family studies are now beginning to elucidate the role of this and other genetic factors in the pathogenesis of RA. We have studied a large family in which the mother and 3 of the 6 children have seropositive RA. One maternal and 1 paternal HLA haplotype contain HLA-DR4. The mother and the 2 children with the maternal DR4 containing haplotype have RA. One sibling inherited neither of the DR4 haplotypes, yet developed RA at age 20. The inheritance of RA in this family illustrates the complexity of the genetic predisposition to this immunologically mediated disorder.

Adult↗