Immune response gene control of collagen reactivity in man: collagen unresponsiveness in HLA-DR4 negative nonresponders is due to the presence of T-dependent suppressive influences
To determine whether the failure to detect collagen reactivity in nonresponders represents an absence of collagen-reactive T cells or a preponderance of suppressive influences, the peripheral blood mononuclear cells from HLA-DR4/sup -/ individuals were subjected to three procedures capable of separating suppressive influences from LIF-secreting cells; irradiation (1000 rad), discontinuous gradient fractionation, and cytolysis with the monoclonal antibody OKT 8. Each procedure resulted in the specific appearance of reactivity to collagen, which was identical to that seen in HLA-DR4/sup +/ individuals with regard to its cellular requirements and antigenic specificity. Addition of unresponsive (i.e., nonirradiated or low-density T cells) to responsive (i.e., irradiated or high-density T cells) autologous populations resulted in specific suppression of collagen reactivity. Radiation-sensitive suppressive influences could not be detected in HLA-DR4/sup +/ collagen responders.These studies indicate that the expression of T-dependent reactivity to collagen in man reflects the net influence of collage-reactive vs collagen-suppressive T cells. Moreover, it is the influence of HLA-D-linked genes on the development of suppressive influences rather than on the development of collagen-reactive, LIF-secreting T cells that serves to distinguish HLA-DR4/sup +/ collagen responders from HLA-DR4/sup -/ collagen nonresponders. (JMT)
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5741763
- Journal Information:
- J. Immunol.; (United States), Vol. 129:5
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BLOOD CELLS
EXTERNAL IRRADIATION
COLLAGEN
IMMUNE REACTIONS
GENETIC CONTROL
CERIUM 137
IMMUNOSUPPRESSION
PATIENTS
RADIOINDUCTION
THYMUS CELLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CERIUM ISOTOPES
CONTROL
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IRRADIATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MATERIALS
NUCLEI
ORGANIC COMPOUNDS
PEST CONTROL
PROTEINS
RADIOISOTOPES
RARE EARTH ISOTOPES
RARE EARTH NUCLEI
SCLEROPROTEINS
SOMATIC CELLS
560151* - Radiation Effects on Animals- Man
550400 - Genetics