Antilymphocyte globulin therapy enhances impaired function of natural killer cells and lymphokine activated killer cells in aplastic anaemia.
MHC-unrestricted cytotoxic lymphocytes, namely natural killer (NK) and lymphokine activated killer (LAK) cells, have been implicated in the regulation of haemopoiesis. To investigate the possible role of these lymphocytes in the pathogenesis of aplastic anaemia (AA), we studied their functions in the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with AA treated with antilymphocyte globulin (ALG). Before treatment, both NK and LAK activities in the PBMC of 25 patients were low (NK = 1.9 +/- 2.1 x 10(3) LU/l) LAK = 4.7 +/- 3.6 x 10(3) LU/l) compared to normal (NK = 6.0 +/- 3.0 x 10(3) LU/l, LAK = 10.0 +/- 3.5 x 10(3) LU/l) or multiply transfused (NK = 7.8 +/- 6.6 x 10(3) LU/l, LAK = 25.2 +/- 13.6 x 10(3) LU/l) controls. The NK and LAK activities in the BMMC in AA patients were not significantly different from those in PBMC. In all patients with low LAK and NK activities pre ALG there was an increase in activity 2-24 weeks after therapy which eventually reached normal levels and which was maintained for up to 2 years. Analysis of lymphocyte phenotypes in AA patients before treatment showed both significantly low mean proportion and absolute numbers of CD16+ cells compared to normals, which increased after therapy. Changes in MHC-unrestricted cytotoxicity and lymphocyte phenotypes post therapy were not correlated with haemopoietic recovery. These data suggest that ALG treatment can enhance the functions of MHC-unrestricted lymphocytes independently from haemopoiesis. It is unlikely that these cells play a role in the pathogenesis of AA.
St Georges Hospital Medical School, London.
A A
AA
Myint
V
V
Malkovska
S
S
Morgan
J
J
Luckit
B
B
Wonke
E C
EC
Gordon-Smith
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy*; D015703:Antigens, CD / Q000032:analysis; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D000961:Antilymphocyte Serum